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ID PMID Title PublicationDate abstract
25435011 Interspinous bursitis is common in polymyalgia rheumatica, but is not associated with spin 2014 Dec 1 INTRODUCTION: Polymyalgia rheumatica (PMR) is a common inflammatory disease in older people characterized by shoulder and/or pelvic girdle, and cervical and, occasionally, lumbar pain. Interspinous bursitis has been suggested as a potential cause of spinal symptoms. We evaluated, by 18 F-fluorodeoxyglucose (FDG) positron emission tomography integrated with computed tomography (PET/CT), the vertebral structures involved in PMR in a cohort of consecutive, untreated patients. METHODS: Sixty-five consecutive patients with PMR were studied. After a standardized physical examination, which included evaluation of pain and tenderness in the vertebral column, they underwent FDG-PET/CT. Sites of increased uptake and their correlation with spontaneous and provoked pain were recorded. For comparison, FDG-PET/CT was performed also in 65 age- and sex-matched controls and in 10 rheumatoid arthritis (RA) patients. RESULTS: The most frequent site of spontaneous and provoked pain was the cervical portion. FDG uptake was more frequent in the lumbar portion than at any other location, and in the cervical rather than in the thoracic portion (P <0.0001). No correlation was found between uptake and spontaneous or provoked pain. There was an association between presence of cervical and lumbar bursitis (r = 0.34, P = 0.007). None of the control patients and one out of ten RA patients showed interspinous bursitis. CONCLUSIONS: Interspinous bursitis is a frequent finding in the lumbar spine of patients with PMR. However, it is not associated with clinical symptoms and can hardly explain the spinal pain reported by the patients. Cervical pain is more frequent than lumbar pain in PMR patients and may be caused by shoulder girdle involvement.
24431284 The plasma cell signature in autoimmune disease. 2014 Jan OBJECTIVE: Production of pathogenic autoantibodies by self-reactive plasma cells (PCs) is a hallmark of autoimmune diseases. We undertook this study to investigate the prevalence of PCs and their relationship to known pathogenic pathways to increase our understanding of the role of PCs in disease progression and treatment response. METHODS: We developed a sensitive gene expression-based method to overcome the challenges of measuring PCs using flow cytometry. Whole-genome microarray analysis of sorted cellular fractions identified a panel of genes, IGHA1, IGJ, IGKC, IGKV4-1, and TNFRSF17, expressed predominantly in PCs. The sensitivity of the PC signature score created from the combined expression levels of these genes was assessed through ex vivo experiments with sorted cells. This PC gene expression signature was used for monitoring changes in PC levels following anti-CD19 therapy, for evaluating the relationship between PCs and other autoimmune disease-related genes, and for estimating PC levels in affected blood and tissue from patients with multiple autoimmune diseases. RESULTS: The PC signature was highly sensitive and capable of detecting a change in as few as 360 PCs. The PC signature was reduced more than 90% in scleroderma patients following anti-CD19 treatment, and this reduction was highly correlated (r = 0.80) with inhibition of collagen gene expression. Evaluation of multiple autoimmune diseases revealed that 30-35% of lupus and rheumatoid arthritis patients had increased levels of PCs. CONCLUSION: This newly developed PC signature provides a robust and accurate method of measuring PC levels in the clinic. Our results highlight subsets of patients across multiple autoimmune diseases who may benefit from PC-depleting therapy.
24330664 Cartilage oligomeric matrix protein-induced complement activation in systemic sclerosis. 2013 INTRODUCTION: Complexes between cartilage oligomeric matrix protein (COMP) and the complement activation product C3b have been found in the circulation of patients with rheumatoid arthritis and systemic lupus erythematosus. In systemic sclerosis (SSc) COMP expression in the skin is upregulated both in lesional and non-lesional skin, which is also reflected in an increased amount of circulating COMP. We investigated the presence of COMP-C3b complexes in serum and skin biopsies of patients with SSc. METHODS: The presence of COMP and COMP-C3b complexes in the serum of 80 patients with limited cutaneous SSc (lcSSc, n = 40) and diffuse cutaneous SSc (dcSSc, n = 40) and 97 healthy controls was measured by ELISA and correlated to different clinical parameters. Samples were collected both at baseline and after three to five years to assess longitudinal changes in COMP-C3b complex levels. Furthermore, skin biopsies from seven patients with dcSSc and three healthy controls were analyzed for expression of COMP and deposition of C3b and IgG. RESULTS: Serum levels of COMP-C3b were found to be elevated in both dcSSc and lcSSc compared to healthy controls and decreased at the second measurement in patients on immunosuppressive therapy. No co-localization of COMP and C3b was found in the skin biopsies, indicating that the COMP-C3b complexes are formed upon release of COMP into the circulation. CONCLUSION: COMP-C3b complexes are found in the serum of patients with SSc. The lack of co-localization between COMP and C3b in the skin suggests that COMP does not drive complement activation in the skin in SSc.
23362188 Similar problem in the activities of daily living but different experience: a qualitative 2014 Mar OBJECTIVE: The aim of the present study was to compare and contrast the concepts of functioning in daily life which were important to patients with different rheumatological conditions. METHOD: The study comprised a qualitative analysis of 44 focus groups in eight European countries, in 229 patients with fibromyalgia, hand osteoarthritis, psoriatic arthritis, rheumatoid arthritis, systemic lupus erythematosus and systemic sclerosis, using the World Health Organization, 2001 International Classification of Functioning, Disability and Health as a framework. Concepts and - where necessary - also sub-concepts and transcripts were combined and compared independently by two researchers who, in case of disagreement, achieved consensus through discussion. RESULTS: Twenty concepts out of 109 (e.g. body image, fatigue, emotional issues, mobility and hand function) were similarly described in all six diseases. However, even if the same concept was mentioned, patients' experiences were different, such as mental AND physical aspects limiting the ability to drive in patients with fibromyalgia compared with ONLY physical problems in all other diseases. Within body functions and structures, several concepts were relevant for certain conditions only. CONCLUSION: A large number of similar problems are mentioned as 'typical' by patients with different rheumatic conditions. These could probably be targeted, using a disease-specific approach, in interventions by non-physician health professionals.
24716217 Clinical spectrum of rheumatologic diseases in a department of rheumatology in Ouagadougou 2014 Mar The aim of this study is to review over a period of 5 years the clinical spectrum of rheumatic diseases seen in a tertiary hospital in Ouagadougou, Burkina Faso. A retrospective study of case records was conducted from March 1, 2006 to March 30, 2011 in the Rheumatology service, Department of Internal Medicine of the University Hospital Yalgado Ouedraogo. Of the 4,084 patients seen, 2,381 were women (58.30%) and 1,703 were men (41.70%). The mean age at disease onset was 42.12 years, ranging from 3 to 92 years. Among the rheumatologic conditions, mechanical and degenerative disorders were the most common, found in 3,053 cases (74.76%). Among these cases, spinal pathology predominated, especially low back pain (19.93 %). The frequency of osteoarthritis was 19.70 % (804 cases) with a predominance of knee osteoarthritis (657 cases). Infectious pathology was dominated by osteoarticular tuberculosis (48 cases), particularly Pott's disease (43.68% of infectious diseases). Among the cases of inflammatory arthritides, rheumatoid arthritis was the leading cause (116 cases or 2.84%). It was followed by spondyloarthropathies in which arthritis related to HIV predominated (21 out of 81 cases). Metabolic diseases were mainly represented by the gout (162 cases or 3.96%) with male predominance. Comorbidities included high blood pressure (46.57%), diabetes mellitus (13.78%), hemoglobinopathies (9.66%), epigastric pain (7.25%), and peptic ulcer confirmed by endoscopy (6.75%). Rheumatology in Burkina Faso is booming. The profile of rheumatologic diseases in Burkina Faso, after 5 years of practice, confirms the diversity and importance of these conditions dominated by a degenerative pathology of the spine and limbs, including infectious diseases such as Pott's disease and the inflammatory and metabolic diseases.
24444433 Methotrexate induces production of IL-1 and IL-6 in the monocytic cell line U937. 2014 Jan 20 INTRODUCTION: Methotrexate (MTX) has been for decades a standard treatment in a wide range of conditions, from malignancies to rheumatoid arthritis (RA). Despite this long experience, the mechanisms of action of MTX remain incompletely understood. Reported immunologic effects of MTX include induction of increased production of some cytokines, an effect that seems to be at odds with the generally anti-inflammatory effects of this drug in diseases like RA. To further elucidate these immune activities, we examined effects of MTX on the human monocytic cell line U937. METHODS: The U937 cell line was treated in vitro with pharmacologic-range concentrations of MTX and effects on production of interleukin (IL)-1, IL-6 and TNF alpha were measured. Changes in gene expression for IL-1 and IL-6 and specificities in the Jun-N-terminal kinase (JNK) signaling pathway including JNK 1, JNK2, JUN and FOS were also determined. The contribution of NF-kB, folate and adenosine pathways to the observed effects was determined by adding appropriate inhibitors to the MTX cultures. RESULTS: MTX mediated a dose-dependent increase in IL-1 and IL-6 in U937 cells, as measured by secreted proteins and levels of gene expression. The increased cytokine expression was inhibited by addition of parthenolide and folinic acid, but not by caffeine and theophylline, suggesting that NF-kB and folates, but not adenosine, were involved in mediating the observed effects. When U937 cells were cultured with MTX, upregulated expression of JUN and FOS, but not JNK 1 or 2, also was observed. CONCLUSIONS: MTX induces expression of proinflammatory cytokines in U937 monocytic cells. These effects might mediate the known toxicities of MTX including pneumonitis, mucositis and decreased bone mineral density.
23956505 Development and treatments of inflammatory cells and cytokines in spinal cord ischemia-rep 2013 During aortic surgery, interruption of spinal cord blood flow might cause spinal cord ischemia-reperfusion injury (IRI). The incidence of spinal cord IRI after aortic surgery is up to 28%, and patients with spinal cord IRI might suffer from postoperative paraplegia or paraparesis. Spinal cord IRI includes two phases. The immediate spinal cord injury is related to acute ischemia. And the delayed spinal cord injury involves both ischemic cellular death and reperfusion injury. Inflammation is a subsequent event of spinal cord ischemia and possibly a major contributor to spinal cord IRI. However, the development of inflammatory mediators is incompletely demonstrated. And treatments available for inflammation in spinal cord IRI are insufficient. Improved understanding about spinal cord IRI and the development of inflammatory cells and cytokines in this process will provide novel therapeutic strategies for spinal cord IRI. Inflammatory cytokines (e.g., TNF- α and IL-1) may play an important role in spinal cord IRI. For treatment of several intractable autoimmune diseases (e.g., rheumatoid arthritis), where inflammatory cytokines are involved in disease progression, anti-inflammatory cytokine antagonist is now available. Hence, there is great potential of anti-inflammatory cytokine antagonist for therapeutic use of spinal cord IRI. We here review the mediators and several possibilities of treatment in spinal cord IRI.
23749673 Immunosuppression and HBV reactivation. 2013 May Hepatitis B virus (HBV) reactivation following immunosuppression is defined by an abrupt rise in HBV replication followed by laboratory signs of hepatocellular injury in a "silent" hepatitis B surface antigen (HBsAg) carrier. Reactivation can also occur, albeit at a lower rate, in patients with occult HBV infection. The clinical presentation of reactivation is variable ranging from an asymptomatic course to severe hepatitis, liver failure, and death. It is most frequently observed in patients with lymphoma treated with rituximab and corticosteroids as well as in patients undergoing stem cell and bone marrow transplantation. Other risk groups include patients with solid tumors, subjects infected with human immunodeficiency virus, organ transplant recipients, and those with autoimmune diseases (i.e., inflammatory bowel disease, rheumatoid arthritis). In cancer patients, HBV reactivation can lead to interruption of chemotherapy with serious impact on prognosis. In HBsAg-positive patients who are candidates for chemotherapy or treatment with biologic agents, preemptive treatment with an antiviral agent such as lamivudine, and lately with the more potent tenofovir or entecavir, has become a standard of care, effectively preventing HBV reactivation. Patients with occult HBV should be monitored for alanine aminotransferase and HBV DNA during the course of immunosuppression. Prompt administration of a potent antiviral agent upon diagnosis of reactivation may be lifesaving in such patients.
23168027 Trapezium prosthetic arthroplasty (silicone, Artelon, metal, and pyrocarbon). 2013 Feb Trapezium prosthetic arthroplasty has been utilized to treat basal joint arthritis for nearly five decades in an attempt to mitigate some of the potential disadvantages of trapeziectomy while preserving range of motion. Implant arthroplasty seeks to preserve joint biomechanics, avoids metacarpal subsidence, and should provide immediate stability. These benefits may lead to improvements in strength, durability, and a decrease in metacarpophalangeal joint hyperextension which can occur subsequent to metacarpal shortening. First generation implants were primarily silicone trapezial spacers. While the use of these implants has been curtailed by their association with silicone synovitis, they still remain an option for low demand, rheumatoid patients. More recently developed synthetic spacers such as Artelon interposition arthroplasties have had results inferior to more established procedures including trapeziectomy. A variety of metal total joint prostheses have been developed and some of the more recent designs have shown good short-term outcomes. There are a number of different pyrocarbon implants that have become more recently available which range from trapezial substitution to non-anatomic hemiarthroplasty. Pyrocarbon arthroplasty offers a number theoretical advantages however early results have been mixed and further long term data is required.
23478887 Arthroscopic ankle arthrodesis in hemophilic arthropathy. 2013 Aug BACKGROUND: Ankle arthrodesis is an accepted treatment for patients with advanced disabling tibiotalar arthritis, mostly in osteoarthritis, rheumatoid, and posttraumatic arthritis. No detailed reports have been published regarding the use of arthroscopy for the treatment of the end-stage hemophilic ankle. The purpose of this article is to report the results of arthroscopic ankle arthrodesis in hemophilic arthropathy of the ankle. METHODS: Ten patients (10 ankle joints) who underwent arthroscopically assisted ankle arthrodesis for the treatment of end-stage hemophilic A arthritis were enrolled in this study. The rate of ankle fusion, incidence of complications, and clinical rating by the Morgan system were analyzed. RESULTS: In this series, the fusion rate was 100%, and patients achieved bone fusion as shown by radiographs. The average time to fusion was 10.5 weeks. Superficial wound infection occurred in 1 patient. According to the Morgan system, there were 8 (80%) good to excellent results and 2 (20%) fair results. All patients were satisfied with the outcome of the operation. CONCLUSIONS: Arthroscopic ankle arthrodesis was an effective alternative to open technique with established advantages in hemophilic arthropathy. LEVEL OF CLINICAL EVIDENCE: Level IV, retrospective case series.
24966908 CD4+CXCR5+ follicular helper T cells in salivary gland promote B cells maturation in patie 2014 OBJECTIVE: To examine amount of CD4+CXCR5+Tfh cells and B cells subsets in salivary gland and peripheral blood from patients with primary Sjogren's syndrome (pSS) and to analyze whether the frequency of CD4+CXCR5+Tfh cells is associated with pSS pathologic process. METHODS: The percentages of CD4+CXCR5+Tfh cells and B cell subsets were examined by flow cytometry. B-lymphocyte chemoattraetant (BLC; also called CXCL13), IL-21, IL-6 from the serum of pSS patients was assessed by polymerase chain reaction-enzyme-linked immunosorbent assay (ELISA). RESULTS: The percentages of CD4+CXCR5+Tfh cells in peripheral blood were increased in pSS patients, but decreased after treatment with glucocorticoid and/or immunosuppressive drugs. Abnormal B cell subsets appeared in salivary and peripheral blood of pSS patients. The frequency of salivary CD4+CXCR5+Tfh cells was positively correlated with CD19+CD27+ memory B cells and CD19+CD27high plasma cells. Also increase of salivary CD19+CD27high plasma cells was positively associated with serum ANA titer of pSS patients. CONCLUSIONS: CD4+CXCR5+Tfh cells are significantly increased in salivary and peripheral blood in pSS patients with aberrant CD19+CD27+ memory B cells and CD19+CD27high plasma cells, suggesting that CD4+CXCR5+Tfh cells may contribute to the pathogenesis of pSS by promoting the maturation of B cells.
24967703 MicroRNA-146a provides feedback regulation of lyme arthritis but not carditis during infec 2014 Jun MicroRNAs have been shown to be important regulators of inflammatory and immune responses and are implicated in several immune disorders including systemic lupus erythematosus and rheumatoid arthritis, but their role in Lyme borreliosis remains unknown. We performed a microarray screen for expression of miRNAs in joint tissue from three mouse strains infected with Borrelia burgdorferi. This screen identified upregulation of miR-146a, a key negative regulator of NF-κB signaling, in all three strains, suggesting it plays an important role in the in vivo response to B. burgdorferi. Infection of B6 miR-146a-/- mice with B. burgdorferi revealed a critical nonredundant role of miR-146a in modulating Lyme arthritis without compromising host immune response or heart inflammation. The impact of miR-146a was specifically localized to the joint, and did not impact lesion development or inflammation in the heart. Furthermore, B6 miR-146a-/- mice had elevated levels of NF-κB-regulated products in joint tissue and serum late in infection. Flow cytometry analysis of various lineages isolated from infected joint tissue of mice showed that myeloid cell infiltration was significantly greater in B6 miR-146a-/- mice, compared to B6, during B. burgdorferi infection. Using bone marrow-derived macrophages, we found that TRAF6, a known target of miR-146a involved in NF-κB activation, was dysregulated in resting and B. burgdorferi-stimulated B6 miR-146a-/- macrophages, and corresponded to elevated IL-1β, IL-6 and CXCL1 production. This dysregulated protein production was also observed in macrophages treated with IL-10 prior to B. burgdorferi stimulation. Peritoneal macrophages from B6 miR-146a-/- mice also showed enhanced phagocytosis of B. burgdorferi. Together, these data show that miR-146a-mediated regulation of TRAF6 and NF-κB, and downstream targets such as IL-1β, IL-6 and CXCL1, are critical for modulation of Lyme arthritis during chronic infection with B. burgdorferi.
24347572 Genetic variation in VTCN1 (B7-H4) is associated with course of disease in juvenile idiopa 2014 Jun OBJECTIVE: The course of disease in juvenile idiopathic arthritis (JIA) is unpredictable with episodes of activity and remission. In order to identify predictive factors, 93 SNPs, JIA subtype, age at onset and ANA status were studied in relation to disease course. METHODS: Genetic and clinical parameters were analysed in a cohort of 272 Caucasian patients with persistent oligoarthritis (n=129), extended oligoarthritis (n=57) and rheumatoid factor negative polyarthritis (n=86). Categories of disease course (remitting (n=65), intermediate (n=96) and unremitting (n=111)) were designed based on the cumulative time spent in active disease in the first 2 years. RESULTS: Univariate analysis revealed association of the course of disease with JIA subtype (p=5.7*10(-5)) and three SNPs; VTCN1 rs10 923 223 (p=4.4*10(-5)), VTCN1 rs12 046 117 (p=0.017) and CDK6 rs42 041 (p=0.038). In a subsequent multivariate ordinal logistic regression analysis, VTCN1 rs10 923 223 (OR 0.41, 95%-CI 0.26 to 0.63) and JIA subtype (OR 3.8, 95%-CI 2.0 to 7.2; OR 2.5, 95%-CI 1.4 to 4.2, for extended oligoarthritis and RF-negative polyarthritis vs persistent oligoarthritis, respectively) were the strongest independent factors for course of disease. CONCLUSIONS: This study provides evidence that VTCN1, encoding B7-H4, is associated with course of disease in selected subtypes of JIA. VTCN1 might be useful in predicting the course of disease.
23875718 Long-term effects of a nurse-led group and individual patient education programme for pati 2014 Apr AIMS AND OBJECTIVES: To investigate the long-term effect of a nurse-led hospital-based patient education programme combining group and individual education for patients with chronic inflammatory polyarthritis. BACKGROUND: Patient education interventions have shown short-term effects, but few studies have investigated whether the effects are sustained for a longer period. DESIGN: Randomised controlled trial. METHODS: Patients with rheumatoid arthritis, psoriatic arthritis and unspecified polyarthritis were randomised to the intervention group (n = 71) or a waiting list (n = 70). Primary outcomes were as follows: Global Well-Being and the Arthritis Self-Efficacy Other Symptoms Subscale. Secondary outcomes were as follows: patient activation, physical and psychological health status, patients' educational needs and a Disease Activity Score (DAS28-3). RESULTS: The intervention group had a statistically significant higher global well-being than the controls after 12 months, mean change score 8·2 (95% CI, 1·6-14·8; p-value = 0·015), but not in the Arthritis Self-Efficacy Other Symptoms Subscale, mean change score 2·6 (95% CI, -1·8 to 7·1; p-value = 0·245). Within each group, analyses showed a statistically significant improvement in DAS28-3, mean change -0·3 (95% CI, -0·5 to -0·1; p-value = 0·001), in the intervention group from baseline to 12 months, but not in the controls. The controls had a statistically significant deterioration in the Arthritis Self-Efficacy Other Symptoms Subscale, mean change -5·0 (95% CI, -8·6 to -1·3; p-value = 0·008), Arthritis Impact Measurement Scales - 2 Social, mean change 0·3 (95% CI, 0·1-0·5; p-value = 0·008), and Hospital Anxiety and Depression Scale total, mean change 1·4 (95% CI, 0·3-2·5; p-value = 0·013). CONCLUSION: A combination of group and individual patient education has a long-term effect on patients' global well-being. RELEVANCE TO CLINICAL PRACTICE: Nurses should consider whether a combination of group and individual patient education for patients with chronic inflammatory polyarthritis is an alternative in their clinical practice. This combination is less time-consuming for the patients, and it includes the benefit of group learning in addition to focusing on patient's individual educational needs.
23190644 Common and specific signatures of gene expression and protein-protein interactions in auto 2013 Mar The aim of this study is to understand intracellular regulatory mechanisms in peripheral blood mononuclear cells (PBMCs), which are either common to many autoimmune diseases or specific to some of them. We incorporated large-scale data such as protein-protein interactions, gene expression and demographical information of hundreds of patients and healthy subjects, related to six autoimmune diseases with available large-scale gene expression measurements: multiple sclerosis (MS), systemic lupus erythematosus (SLE), juvenile rheumatoid arthritis (JRA), Crohn's disease (CD), ulcerative colitis (UC) and type 1 diabetes (T1D). These data were analyzed concurrently by statistical and systems biology approaches tailored for this purpose. We found that chemokines such as CXCL1-3, 5, 6 and the interleukin (IL) IL8 tend to be differentially expressed in PBMCs of patients with the analyzed autoimmune diseases. In addition, the anti-apoptotic gene BCL3, interferon-γ (IFNG), and the vitamin D receptor (VDR) gene physically interact with significantly many genes that tend to be differentially expressed in PBMCs of patients with the analyzed autoimmune diseases. In general, similar cellular processes tend to be differentially expressed in PBMC in the analyzed autoimmune diseases. Specifically, the cellular processes related to cell proliferation (for example, epidermal growth factor, platelet-derived growth factor, nuclear factor-κB, Wnt/β-catenin signaling, stress-activated protein kinase c-Jun NH2-terminal kinase), inflammatory response (for example, interleukins IL2 and IL6, the cytokine granulocyte-macrophage colony-stimulating factor and the B-cell receptor), general signaling cascades (for example, mitogen-activated protein kinase, extracellular signal-regulated kinase, p38 and TRK) and apoptosis are activated in most of the analyzed autoimmune diseases. However, our results suggest that in each of the analyzed diseases, apoptosis and chemotaxis are activated via different subsignaling pathways. Analyses of the expression levels of dozens of genes and the protein-protein interactions among them demonstrated that CD and UC have relatively similar gene expression signatures, whereas the gene expression signatures of T1D and JRA relatively differ from the signatures of the other autoimmune diseases. These diseases are the only ones activated via the Fcɛ pathway. The relevant genes and pathways reported in this study are discussed at length, and may be helpful in the diagnoses and understanding of autoimmunity and/or specific autoimmune diseases.
25535746 Accumulation of self-reactive naïve and memory B cell reveals sequential defects in B cel 2014 Sjögren's syndrome (SS) is an autoimmune disease characterised by breach of self-tolerance towards nuclear antigens resulting in high affinity circulating autoantibodies. Although peripheral B cell disturbances have been described in SS, with predominance of naïve and reduction of memory B cells, the stage at which errors in B cell tolerance checkpoints accumulate in SS is unknown. Here we determined the frequency of self- and poly-reactive B cells in the circulating naïve and memory compartment of SS patients. Single CD27-IgD+ naïve, CD27+IgD+ memory unswitched and CD27+IgD- memory switched B cells were sorted by FACS from the peripheral blood of 7 SS patients. To detect the frequency of polyreactive and autoreactive clones, paired Ig VH and VL genes were amplified, cloned and expressed as recombinant monoclonal antibodies (rmAbs) displaying identical specificity of the original B cells. IgVH and VL gene usage and immunoreactivity of SS rmAbs were compared with those obtained from healthy donors (HD). From a total of 353 VH and 293 VL individual sequences, we obtained 114 rmAbs from circulating naïve (n = 66) and memory (n = 48) B cells of SS patients. Analysis of the Ig V gene repertoire did not show significant differences in SS vs. HD B cells. In SS patients, circulating naïve B cells (with germline VH and VL genes) displayed a significant accumulation of clones autoreactive against Hep-2 cells compared to HD (43.1% vs. 25%). Moreover, we demonstrated a progressive increase in the frequency of circulating anti-nuclear naïve (9.3%), memory unswitched (22.2%) and memory switched (27.3%) B cells in SS patients. Overall, these data provide novel evidence supporting the existence of both early and late defects in B cell tolerance checkpoints in patients with SS resulting in the accumulation of autoreactive naïve and memory B cells.
24694497 Autoimmune myelofibrosis accompanied by Sjögren's syndrome in a 47, XXX/46, XX mosaic wom 2014 This report describes a patient with autoimmune myelofibrosis accompanied by Sjögren's syndrome (SS). A 36-year-old woman was admitted due to petechiae, purpura, gingival bleeding, dyspnea on exertion, and a lack of concentration. She had pancytopenia and was diagnosed with SS. A bone marrow study showed hypercellular marrow with reticulin fibrosis. Lymphocytic infiltrates and aggregates composed of a mixture of T and B cells in the marrow were also observed. A chromosomal analysis of the marrow cells showed 47, XXX and an analysis of peripheral lymphocytes revealed 47, XXX/46, XX mosaic results. The patient's cytopenia resolved following treatment with oral prednisolone.
24593171 The role of cytotoxic T cells in IgG4-related dacryoadenitis and sialadenitis, the so-call 2014 Nov OBJECTIVES: Immunoglobulin (Ig) G4-related dacryoadenitis and sialadenitis, the so-called Mikulicz's disease (MD), is a chronic inflammatory disease. However, little is known about its pathogenesis and pathological condition. In the present study, we used immunohistological techniques to compare the roles of cytotoxic T lymphocytes (CTLs) in MD and primary Sjogren's syndrome (SS). We examined the state of CTLs [cytotoxic granule-positive rate and programmed death-1 (PD-1) expression rate] in the salivary glands. METHODS: The study samples comprised 12 submaxillary glands from untreated MD patients and 12 labial glands from SS patients. We performed immunofluorescence and multicolor immunofluorescence to stain CD8, perforin (PRF), granzyme B (GZMB), and PD-1. We measured the total number of CTLs as well as the PRF(+)CTLs, GZMB(+)CTLs, and PD-1(+)CTLs. RESULTS: We found that the degree of infiltration of CTLs was equal in MD and SS, but the rate of CTLs with cytotoxic granules, especially PRF, in MD was less than in SS. In addition, the frequency of PD-1(+)CTLs in MD was higher than that in SS. CONCLUSIONS: Cytotoxic granule-positive CTLs were in the minority in D salivary glands, and this regulation might relate to PD-1 signals like the state of exhaustion and anergy.
23920005 T helper subsets in Sjögren's syndrome and IgG4-related dacryoadenitis and sialoadenitis: 2014 Jun IgG4-related disease (IgG4-RD) is a systemic disease characterized by the elevation of serum IgG4 and infiltration of IgG4-positive plasma cells in multiple target organs, including the pancreas, kidney, biliary tract and salivary glands. In contrast, Mikulicz's disease (MD) has been considered a subtype of Sjögren's syndrome (SS) based on histopathological similarities. However, it is now recognized that MD is an IgG4-RD distinguishable from SS and called as IgG4-related dacryoadenitis and sialoadenitis (IgG4-DS). Regarding immunological aspects, it is generally accepted that CD4+ T helper (Th) cells play a crucial role in the pathogenesis of SS. Since it is well known that IgG4 is induced by Th2 cytokines such as interleukin (IL)-4 and IL-13, IgG4-DS is speculated to be a unique inflammatory disorder characterized by Th2 immune reactions. However, the involvement of Th cells in the pathogenesis of IgG4-DS remains to be clarified. Exploring the role of Th cell subsets in IgG4-DS is a highly promising field of investigation. In this review, we focus on the selective localization and respective functions of Th cell subsets and discuss the differences between SS and IgG4-DS to clarify the pathogenic mechanisms of these diseases.
23717383 Serum levels of beta2-microglobulin and free light chains of immunoglobulins are associate 2013 OBJECTIVES: To analyze the clinical and immunological characteristics at enrollment in a large prospective cohort of patients with primary Sjögren's syndrome (pSS) and to investigate the association between serum BAFF, beta2-microglobulin and free light chains of immunoglobulins and systemic disease activity at enrollment. METHODS: Three hundred and ninety five patients with pSS according to American-European Consensus Criteria were included from fifteen centers of Rheumatology and Internal Medicine in the "Assessment of Systemic Signs and Evolution of Sjögren's Syndrome" (ASSESS) 5-year prospective cohort. At enrollment, serum markers were assessed as well as activity of the disease measured with the EULAR Sjögren's Syndrome Disease Activity Index (ESSDAI). RESULTS: Patient median age was 58 (25(th)-75(th): 51-67) and median disease duration was 5 (2-9) years. Median ESSDAI at enrollment was 2 (0-7) with 30.9% of patients having features of systemic involvement. Patients with elevated BAFF, beta2-microglobulin and kappa, lambda FLCS had higher ESSDAI scores at enrollment (4 [2]-[11] vs 2 [0-7], P = 0.03; 4 [1]-[11] vs 2 [0-7], P< 0.0001); 4 [2]-[10] vs 2 [0-6.6], P< 0.0001 and 4 [2-8.2] vs 2 [0-7.0], P = 0.02, respectively). In multivariate analysis, increased beta2-microglobulin, kappa and lambda FLCs were associated with a higher ESSDAI score. Median BAFF and beta2-microglobulin were higher in the 16 patients with history of lymphoma (1173.3(873.1-3665.5) vs 898.9 (715.9-1187.2) pg/ml, P = 0.01 and 2.6 (2.2-2.9) vs 2.1 (1.8-2.6) mg/l, P = 0.04, respectively). CONCLUSION: In pSS, higher levels of beta2-microglobulin and free light chains of immunoglobulins are associated with increased systemic disease activity.