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ID PMID Title PublicationDate abstract
33061632 Simultaneous Presentation of Leukemic Non-Nodal Mantle Cell Lymphoma and Gamma-Delta T-Lar 2020 The peculiar features of T-cell large granular lymphocytic leukemia (T-LGLL) are its association with autoimmune disorders (particularly with rheumatoid arthritis (RA)) and a broad spectrum of B-cell lymphoproliferative disorders. However, association of T-LGLL with mantle cell lymphoma (MCL) is extremely rare. Here, we describe a case of an 80-year-old man admitted with suspected Felty's syndrome. The blood count showed white blood cells at 2.2×10(9)/L, with 3% neutrophils, 88% lymphocytes, and at 0.66×10(9)/L LGLs. The spleen had been removed 43 months prior to the admission due to suspected B-cell splenic lymphoma. Re-examination of the spleen revealed cyclin D1+ and SOX11- lymphocytes in the inner part of the unexpanded mantle zones of the white pulp follicles, thus displaying a so-called in situ histologic pattern of MCL, and in small clusters in the red pulp. The splenic cords were moderately expanded by lymphocytes expressing CD3, TIA1, and granzyme B but not CD4 and CD8. Monoclonal rearrangements of the immunoglobulin heavy chain gene and the T-cell receptor (TCR) gamma and delta chain genes, polyclonal rearrangements of the TCR beta chain gene, mutation of the signal transducer and activator of transctiption 3  gene (c.1940A>T; p.N647I), and t(11;14)(q13;q32) translocation were identified in the spleen sample. Flow cytometry of bone marrow revealed a population of TCR γδ+, CD3+, CD4-, CD5-, CD7+, CD8-, CD16-, CD56-, and CD57- lymphocytes. Fragment analysis demonstrated identical TCR gene clonal rearrangement patterns in the spleen and bone marrow samples. In this study, we describe the first case of simultaneous presentation of γδ T-LGLL and leukemic non-nodal MCL (L-NN-MCL) in a patient with RA and present morphological findings of L-NN-MCL in the spleen.
32505641 The Association Between Interleukin-6 Promoter Polymorphisms and Rheumatoid Arthritis by E 2020 Jun 3 OBJECTIVE: We performed a meta-analysis to determine the effect Interleukin-6 (IL-6) promoter polymorphism (-174 G>C, -572 G>C, and -597 G>A) have on the development rheumatoid arthritis (RA) by ethnicity. MATERIAL AND METHODS: PubMed, EBSCO, LILACS, and Scopus databases were searched for studies exploring the association between any IL6 polymorphisms and RA until November 2018. Genotype distributions were extracted and, depending on the level heterogeneity, determined by the ψ(2)-based Q test and the Inconsistency Index (I(2)), fixed-effects or random-effects models were used to calculate pooled odds ratios (ORs) with 95% confidence intervals (95%CIs) for the heterozygous, homozygous, dominant, recessive, and allelic genetic models. RESULTS: From 708 identified publications, 33 were used in this analysis. For the -174 polymorphism, Asians (OR(heterozygous)=7.57, 95%CI: 2.28-25.14, OR(homozygous)=5.84, 95%CI: 2.06-16.56, OR(dominant)=7.21, 95%CI: 2.30-22.63, OR(recessive)=5.04, 95%CI: 1.78-14.28, OR(allelic)=6.60, 95%CI: 2.26-19.28, p<.05) and Middle East countries (OR(heterozygous)=2.30, 95%CI: 1.10-4.81, OR(dominant)=2.27, 95%CI: 1.22-4.22, OR(allelic)=2.29, 95%CI: 1.24-4.23, p<.05) were associated with a significant risk of developing RA. Whereas, for Latinos, the C-allele was associated with a benefit (OR(homozygous)=0.26, 95%CI: .08-.82, OR(recessive)=.25, 95%CI: .08-.80, p<.05). For the -572 polymorphism, Asians demonstrated a significant association for the homozygous and recessive genetic models (8 studies, OR(homozygous)=1.56, 95%CI: 1.16-2.09, OR(recessive)=1.63, 95%CI: 1.08-2.45, p<.05). For the -597 polymorphism, no association was observed. CONCLUSIONS: Here, the -174 G>C polymorphism increased the risk of developing RA in Asians and Middle East populations. Interestingly, for Latinos, the polymorphism was associated with a benefit. For the -572 polymorphism, only the Asian population showed an increased risk of developing RA for the CC genotype.
32486012 Identification of Novel Native Autoantigens in Rheumatoid Arthritis. 2020 May 29 The majority of patients diagnosed with rheumatoid arthritis (RA) have developed autoantibodies against neoepitopes in proteins that have undergone post-translational modification, e.g., citrullination or carbamylation. There is growing evidence of their molecular relevance and their potential utility to improve diagnosis, patient stratification, and prognosis for precision medicine. Autoantibodies reacting to native proteins may also have a role in RA pathogenesis, however, their reactivity patterns remain much less studied. We hypothesized that a high-density protein array technology could shed light onto the normal and disease-related autoantibodies produced in healthy and RA patient subgroups. In an exploratory study, we investigated the global reactivity of autoantibodies in plasma pools from 15 anti-cyclic citrullinated peptide (CCP)-positive and 10 anti-CCP-negative RA patients and 10 healthy donors against more than 1600 native and unmodified human proteins using a high-density protein array. A total of 102 proteins recognized by IgG autoantibodies were identified, hereof 86 were recognized by antibodies from CCP-positive RA patients and 76 from anti-CCP-negative RA patients, but not by antibodies from healthy donors. Twenty-four of the identified autoantigens have previously been identified in synovial fluid. Multiple human proteins in their native conformation are recognized by autoantibodies from anti-CCP-positive as well as anti-CCP-negative RA patients.
32118001 Enalapril Influence on Arterial Stiffness in Rheumatoid Arthritis Women: A Randomized Clin 2019 Introduction: Cardiovascular parameters disruption can be found in patients at early stages of rheumatoid arthritis (RA). The primary endpoint of this study was the reduction of arterial stiffness in RA patients without traditional cardiovascular risk factors or previous comorbidities, measured by cardio-ankle vascular index (CAVI) through the enalapril intervention. The secondary endpoints were the enalapril influence on carotid femoral pulse wave velocity (cfPWV), carotid intima media thickness (cIMT), carotid artery distensibility (cDistensibility), Young's incremental elastic modulus (Einc)]. Materials and Methods: Fifty-three patients were enrolled in a clinical, randomized, closed-label trial. The subjects were randomly assigned into two groups: One receiving 5 mg of enalapril (27) or placebo (26), both twice a day. The drug was acquired at Victory Enterprises®. The placebo was kindly provided by the Universidad de Guadalajara (UdeG), as well as the blinding into two groups: A and B. Enalapril and placebo were packed into bottles without labeling. Clinical assessment included a structured questionnaire to gather demographic and clinical variables as well as determination of CAVI, cfPWV, cIMT, carotid artery distensibility and Einc. The whole set of evaluations were analyzed at the baseline and at the end of 12 weeks of intervention. Results: The CAVI measurement at baseline was 7.1 ± 1.4 and increased up to 7.5 ± 1.2 at the end of 12 weeks. Meanwhile, the enalapril group was as follows: 7.4 ± 1.2 and at the of intervention, reduced to 7.1 ± 0.9. A reduction in delta CAVI of 0.21 in the enalapril intervention group was found. In contrast, an increase of 0.39 was observed in the placebo group. The delta CAVI reduction was not influenced by age or peripheral systolic blood pressure (pSBP). Discussion: Enalapril seems to be effective in CAVI reduction in RA patients. The effect of enalapril intervention on arterial stiffness translated to the clinical context might be interpreted as a reduction of 6.4 years of arterial aging. Trial Registration: The protocol was approved by the Institutional Review Board with the register CI-0117 from UdeG, and 0211/18 from Hospital Civil "Dr. Juan I. Menchaca", Secretaría de Salud Jalisco: DGSP/DDI/D.INV.28/18 and retrospectively registered at ClinicalTrials.gov Protocol Registration and Results System: NCT03667131.
33213129 Psoriatic spondyloarthritis and Sjögren syndrome: a casual association? 2020 Nov 19 The association between Sjögren syndrome (SS) and psoriatic arthritis (PsA) is rare. Herein, we report a case of SS in a PsA patient with the mutilans variant. A 67-year old woman developed PsA with progressive articular destruction up to the typical deformation of 'telescoping fingers' in the distal phalanges. Psoriatic onychopathy presented ten years after the osteolytic damage in the hands. This late appearance led to delayed diagnosis and therapy, and, consequently, worsened the articular destruction. Thereafter, the patient developed a typical SS with clinical symptoms, such as xerophthalmia and xerostomia. This diagnosis was confirmed by positive diagnostic tests, such as Schirmer test, ANA, and anti-SSA/Ro and anti-SSB/La antibodies. A potential association between the two diseases is discussed.
32495525 Tear Osmolarity and Matrix Metallopeptidase-9 in Dry Eye Associated with Sjögren's Syndro 2020 Jun PURPOSE: To evaluate the correlations between tear osmolarity and matrix metallopeptidase-9 (MMP-9) and dry eye (DE) indices in patients with DE associated with Sjögren's syndrome (SS). METHODS: Sixty-three patients with DE associated with SS who underwent tear analysis were included. DE tests performed were ocular surface disease index, tear break-up time, Schirmer's test, ocular staining score, and tear osmolarity and MMP-9 tests. Correlations between tear osmolarity and DE indices, differences between patients with abnormal and normal tear osmolarity, and those between positive and negative MMP-9 patients were analyzed. Patients were classified into four groups according to tear osmolarity and MMP-9 results, and between-group differences were analyzed (group 1: abnormal tear osmolarity, MMP-9 positive; group 2: abnormal tear osmolarity, MMP-9 negative; group 3: normal tear osmolarity, MMP-9 positive; group 4: normal tear osmolarity, MMP-9 negative). RESULTS: Mean age of patients was 54.2 ± 13.9 years, and 96.2% were female. Thirty-five patients had abnormal tear osmolarity and 40 patients were MMP-9 positive. DE indices differed between groups with abnormal and normal tear osmolarity (p < 0.01), but not between positive and negative MMP-9 groups. There were 22 patients in group 1, 13 in group 2, 18 in group 3, and 10 in group 4. Compared to group 4, tear break-up time was shorter in groups 1 (p < 0.01) and 2 (p = 0.02). Schirmer's test values in group 1 were lower than those in group 4 (p = 0.03). Ocular staining score was higher in groups 1 (p < 0.01) and 2 (p < 0.05) than in group 4. CONCLUSIONS: Tear osmolarity was correlated with ocular surface indices in DE associated with SS. Combination of tear osmolarity and MMP-9 test results may be helpful to determine the severity of DE associated with SS.
32076706 Sjögren Syndrome in Primary Salivary Gland Lymphoma. 2020 May 5 OBJECTIVES: Sjögren syndrome (SS) is considered as a major etiologic factor for primary salivary gland lymphoma (SGL). However, the percentage of SGL that is caused by SS (and thus the real impact of SS on SGL epidemiology) is unclear. We aimed to assess the prevalence of SS in patients with SGL through a systematic review and meta-analysis. METHODS: Electronic databases were searched for studies assessing the presence of SS in patients with SGL. Pooled prevalence of SS in SGL was calculated, with a subgroup analysis based on histotype (mucosa-associated lymphoid tissue [MALT] vs non-MALT). RESULTS: Sixteen studies with 665 SGLs were included. Pooled prevalence of SS in SGL was 18.2%, with high heterogeneity among studies. In MALT SGL, the prevalence of SS was 29.5%, with moderate heterogeneity. In non-MALT SGL, the prevalence of SS was 0%, with null heterogeneity. CONCLUSIONS: SS seems to be responsible for a significant but minor portion of SGLs. SS appears involved in MALT-type SGL but not in other histotypes.
32075510 Altered hippocampal functional connectivity in primary Sjögren syndrome: a resting-state 2020 Apr Structural and metabolic abnormalities in the hippocampus have been associated with the pathophysiological mechanism of central nervous system involvement in primary Sjögren syndrome (pSS). Nevertheless, how hippocampal function is altered in pSS remains unknown. The purpose of our study is to investigate the alterations in hippocampal functional connectivity (FC) in pSS by using resting-state functional magnetic resonance imaging (rs-fMRI). Thirty-eight patients with pSS and 38 age- and education level-matched healthy controls (HCs) underwent magnetic resonance imaging examination. Prior to each MRI examination, neuropsychological tests were performed. Left and right hippocampal FCs were analyzed by using seed-based whole-brain correlation and compared between pSS and HCs. Spearman correlation analysis was performed between the z-value of hippocampal FC in brain regions with significant difference between the two groups and neuropsychological tests/clinical data in pSS. Compared with the controls, the patients with pSS showed decreased hippocampal FC between the left hippocampus and the right inferior occipital gray (IOG)/inferior temporal gray (ITG), as well as between the right hippocampus and right IOG/middle occipital gray (MOG), left MOG, and left middle temporal gray. In addition, increased hippocampal FCs were detected between the left hippocampus and left putamen, as well as between the right hippocampus and right cerebellum posterior lobe. Moreover, the visual reproduction score positively correlated with the FC between right hippocampus and right IOG/MOG. The white matter hyperintensity score negatively correlated with the FC between left hippocampus and right IOG/ITG. In conclusion, patients with pSS suffered decreased hippocampal FC mainly sited in the occipital and temporal cortex with right hippocampal laterality. Altered hippocampal FC might be a potential biomarker in detecting brain function changes and guiding neuroprotection in pSS.
31661424 Polyneuropathy and the sural/radial sensory nerve action potential ratio in primary Sjögr 2020 Jan Objectives: Polyneuropathy is the most common neurological complication in primary Sjögren's syndrome (pSS). A ratio of sural nerve and superficial radial nerve sensorial action potential amplitudes (SRARs) of <0.4 is an indicator for early axonal neuropathy. We evaluated the polyneuropathies and SRARs in pSS patients.Method: Fifty-two female patients who were diagnosed with pSS according to the European-American Consensus Criteria and 45 healthy controls were enrolled. Nerve conduction studies were performed to diagnose polyneuropathy. Sensory axonal polyneuropathy was diagnosed in three patients, so SRARs were compared in 49 patients and 50 healthy controls.Results: Fifty-two patients with pSS underwent nerve conduction tests. The sural sensory nerve action potential (SNAP) was <6 µV in threepatients and they were diagnosed with sensory axonal neuropathy. SRARs were evaluated in 49 female patients, with a mean age of 51.98 ± 10.79 years and 50 healthy controls with a mean age of 50.52 ± 12.55 years. The mean disease duration was 7.59 ± 6.17 years. The SRAR values were different between the patient and control groups. SRAR was <0.4 in 20.4% of the patient group and <0.4 in 6% of the control group. The SRAR value was not statistically different within the patient group based on anti-Ro and anti-La.Discussion: The potential for neurological involvement in patients with pSS who have no signs or injury should be evaluated because nervous system involvement in pSS is a negative prognostic factor. SRAR in patients with pSS can be used as a marker for the early detection of axonal neuropathy.
32139667 Depletion of ID3 enhances mesenchymal stem cells therapy by targeting BMP4 in Sjögren's s 2020 Mar 5 Mesenchymal stem cell (MSCs) transplantation has been used to treat Sjögren's syndrome (SS) based on the immunoregulatory properties of MSCs. However, the effectiveness need improving and its underlying intrinsic mechanisms remain largely unknown. Here, we show that Id3 is upregulated in bone marrow-derived MSCs (BMMSCs) isolated from NOD/ShiLtJ mice, a widely used SS model, compared with ICR mice as control, suggesting that it functions in SS development and therapy. Transplantation of Id3-deficient BMMSCs rescues salivary gland function more effective than wild-type BMMSCs in NOD/ShiLtJ mice. Mechanistically, we show that ID3 negatively regulated BMP4 expression by preventing binding of basic helix-loop-helix protein E2A to the promoter of the Bmp4 gene. BMP4 in turn promoted PGE2 production in MSCs, and exhibited enhanced suppressive activities of T-cell proliferation and Th1 differentiation. Importantly, BMMSCs from SS patients showed significantly lower BMP4 and PGE2 expression than those from healthy individuals. Taken together, our findings revealed the targeting Id3 may be therapeutically useful for improving MSC immunoregulation and effectiveness of MSCs therapy for SS.
32195754 Differential Diagnosis of Sjögren Versus Non-Sjögren Dry Eye Through Tear Film Biomarker 2020 Aug PURPOSE: Systemic implications necessitate the identification of dry eye patients with Sjögren syndrome (SS). This study aims to explore the utility of tear MUC5AC and inflammatory cytokine levels in the differential diagnosis of SS-related dry eye. METHODS: A prospective, observational, case-control study was conducted on 62 patients (those with a definitive diagnosis of SS dry eye, non-SS dry eye, and age-matched healthy controls with no dry eye). Clinical evaluations included the following tests in the order listed here: noninvasive tear break-up time, osmolarity, tear sampling, Schirmer test without anesthesia, and ocular surface staining (lissamine green for conjunctiva and fluorescein for cornea). Tear MUC5AC levels were assessed with enzyme-linked immunosorbent assay, and cytokines [interferon-gamma, tumor necrosis factor alpha, interleukin (IL)-6, IL-17a, IL-1β, IL-8, IL-10, and IL-12p70] were measured using a Luminex assay in a masked fashion. RESULTS: The Bulbar conjunctival lissamine green staining score was significantly greater in patients or controls with SS versus non-SS dry eye. This greater conjunctival staining was associated with a reduction in tear MUC5AC (B = -17.8 ng/mL, 95% confidence interval = -31.8 to -3.9, P = 0.01). Among the tear cytokines, a significant association was found between IL-8 levels (hazard ratio [HR] = 1.002, 95% confidence interval = 1.000-1.003, P = 0.03) and SS diagnosis. When patients were stratified based on tear MUC5AC levels, significantly increased tear IL-8 levels were detected in patients with SS dry eye but not with non-SS dry eye, in comparison with healthy controls. CONCLUSIONS: Tear levels of goblet cell-specific MUC5AC combined with IL-8 can potentially serve as a useful biomarker for differential diagnosis of SS dry eye from non-SS dry eye.
31199565 American Indians Have a Higher Risk of Sjögren's Syndrome and More Disease Activity Than 2020 Aug OBJECTIVE: To describe the clinical and serologic manifestations of Sjögren's syndrome (SS) in ethnic groups of the US. METHODS: This was a cross-sectional study of 648 patients with primary SS: 20 African American (AA), 164 American Indian (AI), 426 European American (EA), and 38 patients of other races evaluated in a multidisciplinary Sjögren's International Collaborative Clinical Alliance research clinic. RESULTS: AA subjects comprised 3.1% of the SS cohort, much lower than the percentage of AA in the state of Oklahoma (P = 3.01 × E - 05), the US (P = 2.24E - 13), or a systemic lupus erythematosus (SLE) cohort at the same institution (P = 4.26 × 10E - 27). In contrast, the percentage of AI in the SS cohort (25.3%) was much higher than expected (P = 3.17E - 09 versus SLE cohort, P = 6.36 - 26 versus Oklahoma, and P = 8.14E - 96 versus US population). The SS classification criteria were similar between AA and EA, but subjects of AI ancestry had lower rates of abnormal tear and salivary flow, as well as anti-Ro/SSA and anti-La/SSB antibodies. Paradoxically, AI had higher levels of disease activity (mean ± SD European League Against Rheumatism Sjögren's Syndrome Disease Activity Index score 3.77 ± 4.78) in comparison to EA (2.90 ± 4.12; P = 0.011) and more extraglandular manifestations affecting mainly the articular and glandular domains. Meanwhile, AA patients were characterized by higher rates of hypergammaglobulinemia (odds ratio [OR] 1.39 [95% confidence interval (95% CI) 1.39-8.65]; P = 0.01), elevated erythrocyte sedimentation rate (ESR) (OR 3.95 [95% CI 1.46-9.95]; P = 0.009), and parotid enlargement (OR 4.40 [95% CI 1.49-13.07]; P = 0.02). CONCLUSION: AI are affected at high rates with SS but present with few classical features, potentially preventing timely diagnosis. In contrast to SLE, SS is infrequent and not more severe among AA, but the triad of hypergammaglobulinemia, increased ESR, and parotid enlargement warrants extra vigilance for lymphomagenesis.
33340821 Drug retention rates of biological agents in adult onset Still's disease. 2021 Feb OBJECTIVES: To assess drug retention rates (DRRs) and reasons for discontinuation of biologic disease-modifying antirheumatic drugs (bDMARDs) in a large monocentric cohort of patients with adult onset Still's disease (AOSD). METHODS: Clinical data of AOSD patients treated with at least one bDMARD and followed up at our Center were retrospectively evaluated. Data about disease duration, number of previous bDMARDs, concomitant treatments, and reasons for therapy discontinuation were collected. Survival curves were examined by the Kaplan-Meier method and compared using a stratified log-rank test. 24-month DRRs were calculated for each bDMARD. Hazard ratio (HR) for previous bDMARD use was evaluated. RESULTS: Forty-two AOSD patients received a total of 79 bDMARD-courses. Anakinra (ANK; n = 41) was the most frequently used bDMARD, followed by tocilizumab (TCZ; n = 21) and Tumor Necrosis Factor inhibitors (TNFi; n = 17). Biologic agents were administered concomitantly with prednisone in all cases (mean dose, 23 ± 18 mg/day) and with csDMARD therapy in 54 (68%) of courses. Thirty-six (46%) treatment courses were discontinued by 24 months. DRRs at 24 months were 62.5% for TCZ, 53.1% for ANK, and 11.8% for TNFi. ANK and TCZ DRRs were similar (p = 0.576), but significantly higher than TNFi (p = 0.015). Previous biologic therapies did not impact DRR (HR 0.73, 95% CI = 0.40 - 1.31, p = 0.288). CONCLUSIONS: In our AOSD study population, 24 months DRRs of TCZ and ANK were similar and significantly higher than the TNFi DRR. Previous use of biologic agents did not affect DRRs.
32504193 Clinical and serological characteristics of seronegative primary Sjögren's syndrome: a co 2021 Jan OBJECTIVES: This study compared the clinical and serological characteristics of seronegative and seropositive primary Sjögren syndrome (pSS) and examined whether current classification criteria for pSS cover seronegative pSS. METHODS: The study group comprised 375 patients (341 women and 34 men) diagnosed with pSS. A clinical diagnosis by an expert rheumatologist was considered the "gold standard" for the diagnosis of pSS. The clinical and serological characteristics of the patients were retrospectively collected from hospital medical files. RESULTS: Fifty-eight of the 375 pSS patients (15.5%) were seronegative for ANA, RF, anti-Ro, and anti-La autoantibodies. Seronegative pSS was diagnosed based on lymphocytic infiltrations in lip biopsy samples. There were no statistically significant differences in terms of patient age, age at diagnosis, sex distribution, clinical features, and laboratory findings between seronegative and seropositive pSS. The frequency of hypergammaglobulinemia was higher in seropositive pSS. The 2016 ACR/ULAR criteria best covered most seronegative pSS cases (84.5%). For seronegative pSS, the agreement between the 2002 AECG, 2012 ACR, and 2016 ACR/EULAR criteria was relatively low. CONCLUSIONS: The clinical features of seronegative pSS (i.e., a lack of four autoantibodies in serum) were similar to those of seropositive pSS. The current classification criteria for pSS should not be used in the diagnosis of seronegative pSS, as the agreement between the different sets of criteria was low, and some patients fell outside the classification. Further clinical and laboratory studies are needed to identify the features that distinguish seronegative pSS. Key Points • Approximately 15% of the pSS patients were seronegative for ANA, RF, anti-Ro, and anti-La autoantibodies. • Seronegative pSS was diagnosed based on lymphocytic infiltrations in lip biopsy samples. • The clinical features of seronegative pSS were similar to those of seropositive pSS. • The current classification criteria for pSS should not be used in the diagnosis of seronegative patients, as the agreement between the different sets of criteria was low, and some patients fell outside the classification.
33095137 Significance of anti-La/SSB antibodies in primary Sjögren's syndrome patients with combin 2020 Jul OBJECTIVES: Immunological parameters exert a relevant diagnostic and prognostic role in primary Sjögren's syndrome (pSS) and may identify specific disease phenotypes. Among disease-associated immunological features, anti-La/SSB are rarely found without concomitant anti-Ro/SSA and their clinical significance in patients with pSS has been poorly investigated. Thus, we aimed to characterise the value of anti-La/SSB analysing clinical and serologic features of a wide cohort of pSS patients with both circulating anti-Ro/SSA and positive salivary gland biopsy (SGB). METHODS: Clinical and serological data of 600 pSS patients with both anti-Ro/SSA and SGB positivity and categorised according to anti-La/SSB status were retrospectively analysed. Comparisons between patients with and without circulating anti-La/SSB were performed. RESULTS: Among the whole cohort, 319 (53%) of patients were anti-La/SSB negative and 281 (47%) were anti-La/SSB positive. Anti-La/SSB positive patients were younger at disease diagnosis and had a longer disease duration. Moreover, anti-La/SSB positive patients had a higher prevalence of hypergammaglobulinaemia and circulating rheumatoid factor and of lymphoproliferative disorders in comparison to seronegative group. At multivariate analysis, hypergammaglobulinaemia (OR=1,7; 95% CI 1.17, 2.43), rheumatoid factor (OR=2.3; 95% CI 1.6, 3.3) and lymphoma (OR=2.6; 95% CI 1.12, 5.96) were identified as independent variables significantly associated with anti-La/SSB positivity. CONCLUSIONS: In patients with pSS and concomitant anti-Ro/SSA and SGB positivity, the presence of anti-La/SSB may help in identifying a disease subset with distinct prognostic features, especially in terms of higher risk of lymphoproliferative complications.
32965698 Evaluation of the Saxon test for patients with hyposalivation without Sjögren's syndrome. 2020 Dec BACKGROUND: Dry mouth is associated with salivary gland hypofunction, which may result from several conditions such as Sjögren's syndrome (SS), head and neck cancers, and side effects of medications. The Saxon test is a useful diagnostic method for hyposalivation in clinical settings. However, previous reports indicate that the test has mostly been used for patients with SS. OBJECTIVE(S): In the present study, we focused on patients with dry mouth who were not diagnosed with SS (patients without SS). METHODS: For patients without SS (n = 302), we examined the factors affecting Saxon test scores using multiple regression analysis. Additionally, we performed a correlation analysis comparing the Saxon test with other diagnostic methods. RESULTS: In 57.6% patients, the Saxon test score was more than 2.00 g/2 min, which is considered negative for hyposalivation. Multiple regression analysis revealed that the age and sex of patients significantly influenced test scores. The mean Saxon test score was less than 2.00 g/2 min in older patients and women. Moreover, the test showed a significant correlation with other methods used to measure salivary flow. CONCLUSION: The Saxon test is useful not only for patients with SS but also for patients without SS.
32896259 Type-III interferons in Sjögren's syndrome. 2020 Jul Primary Sjögren's syndrome (pSS) is a systemic autoimmune disease characterised by aberrant activation of innate and adaptive immune responses. Part of this hyper-activation is due to the interferon (IFN) system. Deregulated expression and activity of the type-I IFN system has been extensively studied in pSS. Type-III interferons (IFNs) are the latest addition to the IFN family, and exhibit potent anti-viral functions, similarly to type-I IFNs. More recently they have started to attract attention as key modulators in the interface of innate and adaptive immunity and chronic inflammation. Deregulated expression of type-III IFNs has been demonstrated in various autoimmune diseases over the last ten years. The scope of this review is to summarise recent findings regarding the biology of type-III IFNs in pSS. We highlight factors that regulate their induction, their downstream effects, their similarities and differences with type-I IFNs and their possible modes of action in Sjögren's syndrome. Finally, we discuss their potential benefits as targets for therapeutic intervention.
33106929 Biologic therapy in Sjögren's syndrome. 2021 Jun Sjögren's syndrome (SS) is a chronic autoimmune disease with complex and diverse clinical manifestations. It is characterized by lymphocyte infiltration of exocrine glands such as the salivary gland and lacrimal gland leading to insufficient secretion of the gland, manifested as dry mouth and dry eyes. In addition, it can involve extraglandular organs and cause systemic damage. The pathogenesis of SS is still unclear. At present, symptomatic treatment is the mainstay and there is a lack of effective therapy. With the development of molecular pathways underlying the pathogenesis of SS, more and more novel biological agents are used to treat SS. We summarized and analyzed the existing evidences on the efficacy of biological treatment of SS and their targets. Analysis of the efficacy of biological therapy and improvement of treatment strategies can help to give full play to its therapeutic advantages.
33081544 Reduced salivary flow and caries status are correlated with disease activity and severity 2020 Oct OBJECTIVE: To analyze the correlations of saliva production and pH value with disease activity, disease severity, and oral health-related quality of life in patients with diffuse cutaneous systemic sclerosis (dcSSc) without concomitant Sjögren's syndrome (SS) or SS-related antibodies. METHODS: This cross-sectional study included 28 patients with dcSSc and matching healthy controls. Sialometric assessment and caries status were compared between the two groups. Clinical and laboratory parameters were used to evaluate disease severity, in accordance with the Medsger Severity Scale. RESULTS: In patients with dsSSc, reduced saliva production and higher pH value were associated with disease activity and severity; moreover, caries status was correlated with SSc disease characteristics, including disease duration and disease severity. Oral health-related quality of life was negatively correlated with mean salivary flow rate. CONCLUSIONS: These findings contradict the existing notion that reduced saliva production in patients with SSc is linked to SS-related antibodies or caused by underlying SS. In addition, patients with dcSSc exhibit elevated risk of cardiovascular disease and invasive dental treatment has been shown to enhance the rates of stroke and heart attack in the general population; therefore, oral health is particularly important in patients with SSc.
32571407 Parenchymal lung disease in adult onset Still's disease: an emergent marker of disease sev 2020 Jun 22 BACKGROUND: Adult-onset Still's disease (AOSD) is a systemic inflammatory disorder of unknown aetiology usually affecting young adults. Interestingly, recent evidence from the juvenile counterpart of AOSD suggested the emergent high fatality rate of lung disease (LD) in these patients. In this work, we aimed to characterise LD in AOSD, to identify associated clinical features and predictive factors, and to describe long-term outcomes of the disease comparing patients with LD and those without. METHODS: A retrospective assessment of prospectively followed patients, from January 2001 to December 2019, was provided to describe the rate of LD in AOSD, associated clinical features and predictive factors, and long-term outcomes. Patients with AOSD, who were included in Gruppo Italiano di Ricerca in Reumatologia Clinica e Sperimentale (GIRRCS) cohort, were assessed. RESULTS: Out of 147 patients included in GIRRCS cohort, 18 (12.25%) patients were reported to be affected by LD, at the time of diagnosis of AOSD, who were characterised by older age, a higher prevalence of myalgia, of lymph node involvement, of pleuritis, and abdominal pain. Furthermore, patients with LD showed higher values of systemic score and ferritin. Among those clinical variables, older age and systemic score were also independently predictors of LD. Chest CT scans were also obtained, and the most common finding was the peripheral consolidations in 8 (44.4%) patients. Finally, a higher mortality rate, of 38.9%, was registered in patients with LD than others, since it was associated with a significant decreased survival rate. CONCLUSIONS: The presence of LD could suggest an emergent cause of mortality in AOSD, as observed in juvenile counterpart recognising a further marker of severity and poor prognosis to be careful evaluated. Patients with LD were also characterised by some clinical features, higher values of systemic score and ferritin than the others, identifying a subset of patients mostly burdened by systemic signs and symptoms. Although specific designed future studies are needed to fully elucidate the significance of LD in AOSD, a more accurate evaluation and management of this feature could improve the long-term outcomes of these patients.