Browse

Search for: rheumatoid arthritis    methotrexate    autoimmune disease    biomarker    gene expression    GWAS    HLA genes    non-HLA genes   

ID PMID Title PublicationDate abstract
27418057 [Clinical spectrum of IgG4-related diseases and the connection to rheumatology]. 2016 Sep Rheumatologist should be familiar with the concept of IgG4-related disease (IgG4-RD). Due to the clinical spectrum IgG4-RD can fall directly within the scope of rheumatology and are often diagnosed primarily by rheumatologists. Furthermore, IgG4RD are relevant differential diagnoses for many other rheumatic conditions. Finally, there are an increasing amount of data suggesting an important role of immunological processes observed in IgG4-RD for other rheumatic diseases.
27115697 [Role of non-coding regulatory ribonucleic acids in chronic inflammatory diseases]. 2016 May Non-coding regulatory ribonucleic acids (RNA), including microRNA, long non-coding RNA and circular RNA, can influence the expression of genes mediating inflammatory processes and therefore affect the course and progression of chronic inflammatory diseases. Recent studies using antisense oligonucleotides suggest that such non-coding regulatory RNAs are suitable as novel therapeutic target molecules for the treatment of inflammatory rheumatic diseases.
26451269 Effectiveness of Certolizumab Pegol in Treating Rheumatoid Arthritis Patients with Persist 2015 We report four cases of successful treatment with certolizumab pegol (CZP) of rheumatoid arthritis (RA) patients with persistent inflamed residual mono- or oligosynovitis resistant to prior TNF-α inhibitors. Although the patients were in a moderate disease activity, a low activity, or a remission of RA, they sustained inflammatory mono-/oligoarthritis even after treatment with prior TNF inhibitors. They were then all treated with CZP and observed in a serial ultrasonography. In all cases, the positive power Doppler signals in the joint have disappeared promptly and all of the patients were able to retain remission in the long term. The treatment of CZP to the refractory mono-/oligoarthritis of inflammatory synovitis in RA patients has not been previously described. The cases suggest that it may be associated with the feature of CZP, possible effective penetration into the site of inflammation.
25983850 Herb Network Analysis for a Famous TCM Doctor's Prescriptions on Treatment of Rheumatoid A 2015 Traditional Chinese Medicine (TCM) doctors always prescribe various herbal formulae tailored to individual patients. However, there is still a lack of appropriate methods to study the rule and potential biological basis underlying the numerous prescriptions. Here we developed an Herb-Compound-Target-Disease coherent network approach to analyze 871 herbal prescriptions from a TCM master, Mr. Ji-Ren Li, in his clinical practice on treatment of rheumatoid arthritis (RA). The core herb networks were extracted from Mr. Li's prescriptions. Then, we predicted target profiles of compounds in core herb networks and calculated potential synergistic activities among them. We further found that the target sets of core herbs overlapped significantly with the RA related biological processes and pathways. Moreover, we detected a possible connection between the prescribed herbs with different properties such as Cold and Hot and the Western drugs with different actions such as immunomodulatory and hormone regulation on treatment of RA. In summary, we explored a new application of TCM network pharmacology on the analysis of TCM prescriptions and detected the networked core herbs, their potential synergistic and biological activities, and possible connections with drugs. This work offers a novel way to understand TCM prescriptions in clinical practice.
25834811 Genetic vectors as a tool in association studies: definitions and application for study of 2015 To identify putative relations between different genetic factors in the human genome in the development of common complex disease, we mapped the genetic data to an ensemble of spin chains and analysed the data as a quantum system. Each SNP is considered as a spin with three states corresponding to possible genotypes. The combined genotype represents a multispin state, described by the product of individual-spin states. Each person is characterized by a single genetic vector (GV) and individuals with identical GVs comprise the GV group. This consolidation of genotypes into GVs provides integration of multiple genetic variants for a single statistical test and excludes ambiguity of biological interpretation known for allele and haplotype associations. We analyzed two independent cohorts, with 2633 rheumatoid arthritis cases and 2108 healthy controls, and data for 6 SNPs from the HTR2A locus plus shared epitope allele. We found that GVs based on selected markers are highly informative and overlap for 98.3% of the healthy population between two cohorts. Interestingly, some of the GV groups contain either only controls or only cases, thus demonstrating extreme susceptibility or protection features. By using this new approach we confirmed previously detected univariate associations and demonstrated the most efficient selection of SNPs for combined analyses for functional studies.
25526913 Bi-specific antibodies with high antigen-binding affinity identified by flow cytometry. 2015 Feb Using conventional approaches, the antigen-binding affinity of a novel format of bi-specific antibody (BsAb) cannot be determined until purified BsAb is obtained. Here, we show that new lipoprotein A (NlpA)-based bacteria display technology, combined with flow cytometry (FCM), can be used to detect antigen-binding affinity of BsAbs, in the absence of expression and purification work. Two formats of BsAb, scFv2-CH/CL and Diabody-CH/CL, specific for human interleukin 1β (hIL-1β) and human interleukin 17A (hIL-17A), were constructed and displayed in Escherichia coli using NlpA-based bacteria display technology. Conversion of these cells to spheroplasts, and their incubation with fluorescently conjugated antigens resulted in the selective labeling of spheroplasts expressing BsAb; enabling their antigen-binding affinity to be analyzed with FCM. The association and dissociation of BsAbs for binding to hIL-1β and hIL-17A were analyzed using FCM-based assays. The results showed that antigen-binding affinity of Diabody-CH/CL was significantly higher than that of scFv2-CH/CL. To confirm these results of FCM-based assays, BsAbs were expressed, purified and subjected to relative affinity measurements, in vitro and in vivo bioactivity analysis. The results showed that Diabody-CH/CL had greater relative affinities for both antigens, resulting in better blocking bioactivities on cellular level and effects on alleviating joint inflammation, and cartilage destruction and bone damage in collagen induced arthritis (CIA) mice model. These results indicate that BsAbs with good antigen-binding affinity can be identified by FCM-based assays without expression and purification work, and the indentified BsAb can serve as a lead compound for further drug development.
27895642 Functional and Structural Characterization of a Novel HLA-DRB1*04:01-Restricted α-Enolase 2016 Antibodies to citrullinated proteins, common in rheumatoid arthritis (RA) patients, are strongly associated to a specific set of HLA-DR alleles including HLA-DRB1*04:01, *04:04, and *01:01. Here, we first demonstrate that autoantibody levels toward the dominant citrullinated B cell epitope from α-enolase are significantly elevated in HLA-DRB1*04:01-positive RA patients. Furthermore, we identified α-enolase-derived T cell epitopes and demonstrated that native and citrullinated versions of several peptides bind with different affinities to HLA-DRB1*04:01, *04:04, and *01:01. The citrulline residues in the eight identified peptides are distributed throughout the entire length of the presented epitopes and more specifically, localized at peptide positions p-2, p2, p4, p6, p7, p10, and p11. Importantly, in contrast to its native version peptide 26 (TSKGLFRAAVPSGAS), the HLA-DRB1*04:01-restricted citrullinated peptide Cit26 (TSKGLFCitAAVPSGAS) elicited significant functional T cell responses in primary cells from RA patients. Comparative analysis of the crystal structures of HLA-DRB1*04:01 in complex with peptide 26 or Cit26 demonstrated that the posttranslational modification did not alter the conformation of the peptide. And since citrullination is the only structural difference between the two complexes, this indicates that the neo-antigen Cit26 is recognized by T cells with high specificity to the citrulline residue.
27752357 Tofacitinib versus methotrexate in rheumatoid arthritis: patient-reported outcomes from th 2016 OBJECTIVES: To compare patient-reported outcomes (PROs) in methotrexate (MTX)-naive patients (defined as no prior treatment or ≤3 doses) receiving tofacitinib versus MTX. METHODS: In the 24-month, phase III, randomised, controlled, ORAL Start trial (NCT01039688), patients were randomised 2:2:1 to receive tofacitinib 5 mg two times per day (n=373), tofacitinib 10 mg two times per day (n=397) or MTX (n=186). PROs assessed included Patient Global Assessment of disease (PtGA), pain, Health Assessment Questionnaire-Disability Index (HAQ-DI), Functional Assessment of Chronic Illness Therapy-Fatigue (FACIT-F) and health-related quality of life (Short Form-36 [SF-36]). RESULTS: PROs improved following tofacitinib and MTX treatment: benefits were sustained over 24 months. Patients receiving tofacitinib reported earlier responses which were significantly different between each tofacitinib dose and MTX at month 3 through month 24. At month 6 (primary end point), significant improvements versus MTX were observed in PtGA, pain, HAQ-DI, SF-36 Physical Component Summary (PCS), 5/8 domain scores and FACIT-F with tofacitinib 5 mg two times per day; all PROs, except SF-36 Mental Component Summary Score and Medical Outcomes Survey-Sleep, with tofacitinib 10 mg two times per day. At month 6, the proportion of patients reporting improvements ≥minimum clinically important difference were significant versus MTX with tofacitinib 5 mg two times per day in PtGA and 3/8 SF-36 domains; and with tofacitinib 10 mg two times per day in PtGA, pain, HAQ-DI, SF-36 PCS, 4/8 domains and FACIT-F. CONCLUSIONS: Patients with rheumatoid arthritis receiving tofacitinib 5 and 10 mg two times per day monotherapy versus MTX reported statistically significant and clinically meaningful improvements in multiple PROs over 24 months; onset of benefit with tofacitinib treatment occurred earlier. TRIAL REGISTRATION NUMBER: NCT01039688.
27747511 Effect of Methotrexate Plus Adalimumab on the Achievement of Rheumatoid Arthritis Therapeu 2016 Jun INTRODUCTION: There is insufficient evidence regarding the appropriate dose of methotrexate (MTX) required to achieve specific treatment goals in patients with rheumatoid arthritis (RA) receiving biologic drugs in Japan. The present study aimed to assess the dose-response effect of MTX in combination with adalimumab (ADA) to achieve low disease activity (LDA) and/or remission at 24 weeks in RA patients. METHODS: This analysis used data of the ADA all-case survey in Japan (n = 7740), and 5494 patients who received ADA and MTX were classified into five groups by weighted average MTX dose (>0-<4, 4-<6, 6-<8, 8-< 10, and ≥10 mg/week). Of the 5494 patients, 3097 with baseline 28-joint disease activity score based on erythrocyte sedimentation rate >3.2 were analyzed for effectiveness by MTX dose. RESULTS: In biologic-naïve patients (n = 1996/3097), LDA/remission rates increased with MTX up to 6-<8 mg/week and then plateaued at higher doses (LDA, p = 0.0440; remission, p = 0.0422). In biologic-exposed patients (n = 1101/3097), LDA/remission rates increased with MTX dose (LDA, p = 0.0009; remission p = 0.0143). The incidences of serious adverse drug reactions (ADRs) and serious infections did not differ by MTX dose, but total ADRs and infections were significantly higher (p < 0.05) with increased MTX doses. CONCLUSION: The appropriate MTX doses in combination with ADA to achieve LDA and/or remission at week 24 were different between biologic-naïve and biologic-exposed patients with RA, suggesting that 8 mg/week of MTX would be enough for biologic-naïve patients. TRIAL REGISTRATION: ClinicalTrials.gov identifier, NCT01076959. FUNDING: AbbVie and Eisai Co., Ltd.
27747583 Randomized Crossover Comparison of Injection Site Pain with 40 mg/0.4 or 0.8 mL Formulat 2016 Dec INTRODUCTION: Adalimumab, an anti-tumor necrosis factor antibody, is currently available in a 40 mg/0.8 mL formulation. The objective of this analysis was to evaluate injection site-related pain, safety, and tolerability of a 40 mg/0.4 mL formulation of adalimumab that had fewer excipients, a smaller volume, and a delivery presentation with a smaller gauge needle, versus the current 40 mg/0.8 mL formulation in patients with rheumatoid arthritis (RA). METHODS: Two identically designed, phase 2, randomized, single-blind, two-period crossover studies were conducted in Belgium and the Czech Republic (Study 1) and Australia, Canada, and Germany (Study 2). In both studies, adults with RA [biologic-naive or current users of 40 mg/0.8 mL adalimumab with an average injection site-related pain rating ≥3 cm on a visual analog scale (VAS; 0-10 cm)] were randomized to receive 40 mg/0.8 mL or 40 mg/0.4 mL adalimumab at visit 1. After 1-2 weeks (depending on patient medication schedule), patients received the other formulation at visit 2. A pain VAS [McGill Pain Questionnaire (MPQ-SF)] and the Draize scale were evaluated immediately after injection and 15 min postinjection. The primary endpoint was immediate pain after injection. RESULTS: 64 and 61 patients were randomized in Studies 1 and 2, respectively. Both studies found a clinically relevant and statistically significant lower immediate pain after injection for the 40 mg/0.4 mL versus the 40 mg/0.8 mL formulation. The mean difference on the VAS for the pooled data (-2.48 cm) was also clinically relevant. Most other endpoints in both studies favored the 40 mg/0.4 mL formulation, and its tolerability and safety profile were consistent with 40 mg/0.8 mL adalimumab. CONCLUSION: A 40 mg/0.4 mL adalimumab formulation was well tolerated and associated with less injection site-related pain than the 40 mg/0.8 mL adalimumab formulation. TRIAL REGISTRATION: ClinicalTrials.gov identifier, NCT01561313 and NCT01502423. FUNDING: AbbVie.
29900980 Serum Vitamin D Level is Inversely Associated With Anti-Cyclic Citrullinated Peptide Antib 2016 Mar OBJECTIVES: This study aims to assess the relationship between serum vitamin D and anti-cyclic citrullinated peptide (anti-CCP) antibody levels, as well as disease activity in patients with newly diagnosed rheumatoid arthritis (RA). PATIENTS AND METHODS: These measurements were conducted between January 2014 and June 2014. Serum 25-hydroxy vitamin D (25-OH-D), anti- CCP antibody, and erythrocyte sedimentation rates were measured in a cohort of 154 patients (66 males, 88 females; mean age 53.5±12.4; range 29 to 79 years) with early RA. A control group of 60 healthy participants (25 males, 35 females; mean age 51.4±10.3; range 25 to 75 years) was only evaluated for serum 25-OH-D levels. Disease activity was measured by calculating the 28-Joint Disease Activity Score. Blood samples were drawn from cubital veins. After centrifugation, serum was collected and stored under minus 20 degrees. RESULTS: Vitamin D deficiency was more prevalent in RA group compared with control group (48.70% vs. 30.00%, p<0.05). Serum 25-OH-D levels were lower in RA group (19.46±8.20 ng/mL) than control group (23.18±6.71 ng/mL) (p<0.05). In the RA group, serum 25-OH-D levels were negatively correlated to anti-CCP antibody levels (rs= -0.360, p<0.001), erythrocyte sedimentation rate (rs= -0.270, p<0.001), age of patients (rs= -0.602, p<0.001), and disease activity (rs= -0.249, p<0.05), respectively. Serum 25-OH-D level did not vary according to sex in the RA group. In control group, females had lower serum 25-OH-D level (p=0.001, rs=0.404). In addition, serum 25-OH-D level was also negatively associated with age in control group (p<0.001, rs= -0.578). There were no differences between RA group and control group in terms of age and sex ratio. CONCLUSION: Serum 25-OH-D level was negatively correlated to anti-CCP antibody level and disease activity, which implied the therapeutic role of serum 25-OH-D in RA.
27784235 Study in Treatment of Collagen-Induced Arthritis in DBA/1 Mice Model by Genistein. 2016 BACKGROUND: This work aimed to evaluate the effects of genistein treatment in Collagen Induced Arthritis (CIA) mouse model. METHODS: CIA was elicited in DBA/1 Mice by an intradermal injection of 100 μL of an emulsion of bovine type II collagen (CII) in isovolumic incomplete Freund's adjuvant (IFA) at the base of the tail. Twenty-one days later, a second injection of CII in IFA was administered at the base of the tail. After the symptoms of arthritis showed in mouse model, we divided animals into two groups according to their clinical symptom scores. The treatment group was intraperitoneally injected daily with genistein (based on the pre-experiment data and literature reported, 5 mg/kg dose was selected and tested) for 12 days, while the control group was injected with phosphate buffered saline. Inflammatory cytokines titer, radiological, and histological observations were completed at different time's points after treatment. CT analysis was conducted 3 months after the treatment to observe the articular structures. Immunohistochemical analysis was performed to investigate the expression and distribution of VEGF in joint tissues. RESULTS: Genistein suppressed the expressions of IL-1β, IL-6 and TNF-α in the serum. Radiological results showed that bone degradation was inhibited by the treatment. Moreover, hematoxylin and eosin staining showed that the degree of inflammation was relieved. In the cartilage area, TRAP stain-positive cells were detected, which was notably reduced in the treatment group compared to the control group. Micro-CT 3D images clearly exhibited that the joint adhered and structures destroyed in the control group with less destruction in the treatment group. Furthermore, genistein suppressed VEGF expression, and blocked angiogenesis in the synovial tissue. CONCLUSION: Our work provides further data regarding the effects of genistein as a potential treatment drug for RA, as well as the role of genistein in the anti-inflammatory pathway in RA therapy.
26491348 Anti-DR5 mAb inhibits proliferation of human fibroblast-like synovial cells and reduces th 2015 BACKGROUND: We have previously reported that anti-death receptor 5 (DR5) monoclonal antibody (mAb) is therapeutically effective in the treatment of rheumatoid arthritis (RA) in a collagen-induced arthritis rat model. However, the molecular mechanism and the effect of anti-DR5 mAb on proapoptotic genes and cytokine secretion in the human fibroblast-like synovial cells (FLS) requires further clarification. This study may provide new evidence for the application of anti-DR5 mAb as a treatment for RA. METHODS: Human FLS were isolated from patients with RA and were treated with anti-DR5 mAb. An MTT assay and flow cytometry were used to detect the induction of apoptosis in vitro. Cytokine secretion by the FLS was detected using the enzyme-linked immunosorbent assay. The mRNA expression was assessed by reverse transcription polymerase chain reaction, and the protein expression was analyzed by Western blot. The apoptotic pathway was investigated further using a caspase inhibition assay. RESULTS: Anti-DR5 mAb-induced apoptosis in human RA FLS in vitro. The protein expressions of caspase-8, -3, and -9 were decreased in human anti-DR5 mAb-treated FLS in a dose-dependent manner through exposure to a caspase inhibitor, indicating that anti-DR5 mAb induction of apoptosis is through the caspase pathway. Decreased levels of tumor necrosis factor-α (TNF-α) and interferon-γ (IFN-γ) were detected after treatment with anti-DR5 mAb in vitro. CONCLUSION: Anti-DR5 mAb may induce apoptosis in human FLS through the caspase pathway and through decreased secretions of TNF-α and IFN-γ.
25861851 Arthroscopically assisted elbow interposition arthroplasty without hinged external fixatio 2015 Jun BACKGROUND: Total elbow arthroplasty is successful in older, lower demand patients but not in the younger, more active individual with severe elbow arthritis. Interposition arthroplasty is an alternative for younger patients who hope to minimize the degree to which arm use is restricted. Interposition arthroplasty traditionally involves release of all ligaments and capsule. As a result, the postoperative care included the use of a hinged external fixator of the elbow to apply distraction and to permit motion during the early phases of healing. We describe a novel surgical technique without a hinged external fixator that allows secure fixation of the interposition graft through arthroscopic assistance and maintains the integrity of the medial collateral ligament with only a takedown and repair of the lateral collateral ligament complex. METHODS: A retrospective chart review was performed to analyze 4 patients with an average age of 57 years who underwent surgery between 2007 and 2011. The patients were also contacted to assess elbow-specific American Shoulder and Elbow Surgeons and Disabilities of the Arm, Shoulder, and Hand scores. RESULTS: The average follow-up was 3.6 years (range, 2.5-6 years), and 1 patient was converted to a total elbow arthroplasty after 2.5 years because of persistent pain. The remaining 3 patients have done well with regard to pain control, stability, and functional use of the operative extremity. There were no postoperative complications. DISCUSSION: On the basis of our small series of patients, an arthroscopically assisted elbow interposition arthroplasty without hinged external fixation can provide satisfactory medium-term outcomes as a salvage procedure for a difficult condition with limited options.
27882124 (5R)-5-hydroxytriptolide (LLDT-8) prevents collagen-induced arthritis through OPG/RANK/RAN 2016 Nov (5R)-5-hydroxytriptolide (LLDT-8) extracts from Tripterygium have anti-inflammatory, antineoplastic and immunity adjustment functions. The present study used a collagen-induced arthritis (CIA) model to evaluate whether LLDT-8 prevents collagen-induced arthritis, and investigated the signaling underlying this. Male Sprague-Dawley rats were induced to generate CIA, mimicking rheumatoid arthritis (RA). The presence of arthritis was determined using RA progression scores. The inflammatory cytokines interleukin (IL)-1β, IL-6 and nuclear factor-κB were detected using enzyme-linked immunosorbent assay kits. Induced nitric oxide synthase (iNOS) and matrix metalloprotease (MMP)-13 protein expression were measured using western blot analysis. Lastly, reverse transcription-quantitative polymerase chain reaction was used to evaluate osteoprotegerin (OPG) and receptor activator of nuclear factor κB (RANK) gene expression. LLDT-8 improved RA progression scores and reduced the incidence and severity of CIA. Furthermore, LLDT-8 administration inhibited collagen-induced inflammation and iNOS protein expression in arthritic rats. The current data indicated that MMP-13 production was suppressed and OPG/RANKL expression was increased by LLDT-8 treatment in the arthritic rat. The present results suggest that LLDT-8 attenuates CIA through OPG/RANK/RANK ligand signaling in a rat model of RA.
27252273 Reactive oxygen homeostasis - the balance for preventing autoimmunity. 2016 Jul Being mainly known for their role in the antimicrobial defense and collateral damage they cause in tissues as agents of oxidative stress, reactive oxygen species were considered "the bad guys" for decades. However, in the last years it was shown that the absence of reactive oxygen species can lead to the development of immune-mediated inflammatory diseases. Animal models of lupus, arthritis and psoriasis revealed reactive oxygen species-deficiency as a potent driver of pathogenesis. On the contrary, in chronic stages oxidative stress can still contribute to progression of inflammation. It seems that a neatly adjusted redox balance is necessary to sustain an immune state that both prevents the development of overt autoimmunity and attenuates chronic stages of disease.
26359543 Interleukin-6 enhances acid-induced apoptosis via upregulating acid-sensing ion channel 1a 2015 Dec The inflammatory cytokine interleukin-6 (IL-6) is a causative agent of rheumatoid arthritis (RA), a chronic inflammatory disease complicated with degenerative arthritic cartilage. However, the precise mechanism of IL-6 on chondrocyte apoptosis is largely unclear. Acid-sensing ion channels (ASICs), a family of extracellular H(+)-activated cation channels, can be transiently activated by extracellular acid and play a pivotal role in acid-induced cell injury. In the present study, to investigate the role of IL-6 in regulating acid-induced articular chondrocyte apoptosis, primary rat articular chondrocytes were subjected to different treatments with or without IL-6 in the presence of acid. The results showed that the mRNA and protein expressions of ASIC1a were significantly increased in articular cartilage and chondrocytes of adjuvant arthritis (AA) rats. IL-6 could dramatically upregulate the level of ASIC1a in a time- and dose-dependent manner, and induce the activation of JAK2, STAT3, ERK, JNK and NF-κB in articular chondrocytes. Moreover, both the respective inhibitors of these signaling pathways and the specific antibody against IL-6 receptor (tocilizumab) could partially abrogate the ASIC1a upregulation induced by IL-6. Furthermore, IL-6 inhibited the cell viability and enhanced LDH release, [Ca(2+)]i elevation, and apoptosis in acid-induced articular chondrocytes, and these changes could be reversed by using psalmotoxin 1(PcTX1), which is the specific antagonist of ASIC1a. In addition, pretreatment with PcTX1 could inhibit the downregulated expression of Bcl-2 and the upregulated expression of Bax induced by IL-6 in acid-induced articular chondrocytes. Taken together, these results indicated that IL-6 could enhance acid-induced articular chondrocyte apoptosis, the mechanism of which might partially be involved with its ability of regulating the activation of ASIC1a-dependent JAK2/STAT3 and MAPK/NF-κB signaling pathways.
27328271 A re-evaluation of anti-NA-14 antibodies in patients with primary Sjögren's syndrome: Sig 2016 Aug Novel autoantibodies against nuclear antigen of 14 kDa (NA-14)/Sjögren's syndrome nuclear antigen-1 (SSNA-1) are predominantly recognized in sera of patients with primary Sjögren's syndrome (pSS). However, the detailed characteristics of the anti-NA-14 antibody remain unknown. Here, we sought to clarify the characteristics of anti-SSNA-1/NA-14 antibodies and the mechanisms of autoantibody production using sera from patients with connective tissue diseases (including pSS), autoimmune sera reacting with standard autoantigens (SS-A/Ro and/or SS-B/La, ds DNA, Scl-70 and Jo-1), and normal healthy controls (NHCs). Anti-NA-14 antibodies were predominantly recognized in sera from patients with pSS and in autoimmune sera reacting with thSS-A/Ro and/or -SS-B/Lo. Indirect immunofluorescence analysis showed that NA-14 was strongly expressed in mitotic-phase cells. Patients with pSS having anti-NA-14 antibodies exhibited significant elevation of serum IP-10 and BAFF compared to that in patients with pSS without anti-NA-14 antibodies and NHCs. Thus, our data demonstrated that anti-NA-14 antibodies could be classified as novel autoantibodies reacting with mitosis-related autoantigens predominantly recognized in pSS. Moreover, interferon-γ played an important role in the production of anti-NA-14 autoantibodies as patients with pSS having anti-NA-14 antibodies exhibited increased serum levels of IP-10 and BAFF.
27246587 Pulmonary manifestations of Sjögren's syndrome. 2016 Jun In 9-20% of cases, Sjögren's syndrome is associated with various respiratory symptoms. The most typical manifestations are chronic interstitial lung disease (ILD) and tracheobronchial disease. The most common manifestation of ILD is nonspecific interstitial pneumonia in its fibrosing variant. Other types of ILD, such as organising pneumonia, usual interstitial pneumonia and lymphocytic interstitial pneumonitis, are rare. Their radiological presentation is less distinctive, and definitive diagnosis may require the use of transbronchial or surgical lung biopsy. Corticosteroid therapy is the mainstay of ILD treatment in Sjögren's syndrome, but the use of other immunosuppressive drugs needs to be determined. ILD is a significant cause of death in Sjögren's syndrome. Tracheobronchial disease is common in Sjögren's syndrome, characterised by diffuse lymphocytic infiltration of the airway. It is sometimes responsible for a crippling chronic cough. It can also present in the form of bronchial hyperresponsiveness, bronchiectasis, bronchiolitis or recurrent respiratory infections. The management of these manifestations may require treatment for dryness and/or inflammation of the airways. Airway disease has little effect on respiratory function and is rarely the cause of death in Sjögren's syndrome patients. Rare respiratory complications such as amyloidosis, lymphoma or pulmonary hypertension should not be disregarded in Sjögren's syndrome patients.
26823888 Primary Sjögren's syndrome accompanied by pleural effusion: a case report and literature 2015 Sjögren's syndrome (SS) is a systemic autoimmune disease characterized by the infiltration of lymphocytes in exocrine glands, specifically the salivary and lacrimal glands, resulting in the typical symptoms of xerophthalmia and xerostomia. SS may be accompanied by pleural effusion when the lung is involved, but this occurrence has been reported in only 10 cases in the literature. We report the case of a 42 year-old woman with severe bilateral pleural effusion for eight years. Primary Sjögren's Syndrome was finally diagnosed based on the presence of xerophthalmia and xerostomia, biopsy of the minor salivary glands, and positive anti-SS-A antibody in the serum and pleural effusion. Biopsy of the parietal pleura through video-assisted thoracoscopy revealed infiltration of lymphocytes. The patient had a long history of pleural effusion without clear etiology. Malignant disease was first suspected because of abnormal density lesion on the left lung and malignant cells found on cytology, but PET-CT revealed no malignant lesion. Examinations did not support infection, malignant tumor, pulmonary sarcoidosis, or other connective tissue diseases. This data could be useful for the future study of pleural effusion in SS.