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B cell activation may result in an increased secretion of immunoglobulin free light chains (FLCs) in autoimmune diseases.To analyse serum FLC levels in patients with rheumatoid arthritis and in those with primary Sjögren's syndrome (pSS).Blood samples were collected from 80 healthy blood donors, 50 patients with rheumatoid arthritis and 139 patients with pSS. Serum FLC level was measured using a new quantitative immunoassay.Mean (standard error (SE)) serum kappa and lambda FLC levels were significantly higher in patients with rheumatoid arthritis and in those with pSS than in controls (kappa : 18.9 (1.1) and 16.3 (1.4) v 10.5 (0.4) mg/l, p0.001 and p = 0.001, respectively; lambda: 16.7 (1.2) and 19.3 (1.5) v 11.6 (0.6) mg/l, p0.001 for both). 18 (36%) patients with rheumatoid arthritis and 31 (22.3%) patients with pSS had abnormal serum FLC levels (increased kappa or lambda levels and abnormal ratio of kappa:lambda). Serum kappa and lambda levels were correlated with other B cell activation markers in both diseases. FLC levels increased with disease activity, because, unlike total gammaglobulin and immunoglobulin G levels, they were significantly correlated with Disease Activity Score 28 in patients with rheumatoid arthritis (p = 0.004 for kappa, p = 0.05 for lambda) and with extraglandular involvement in pSS (p = 0.01 for kappa, p = 0.04 for lambda).FLC levels are increased and correlate with disease activity in patients with rheumatoid arthritis and in those with pSS, two diseases in which increased risk of lymphoma could result from persistent B cell activation and disease activity. Further studies are required to determine whether FLC assessment could represent a relevant biomarker for response to treatment (especially B cell depletion) and for the risk of lymphoma in autoimmune diseases.

Background The presence of anti-Ku antibody is associated with a wide variety of clinical manifestations and various outcomes. Objectives We attended to refine anti-Ku associated disease by identifying subgroups of Ku-positive patients with similar clinico-biological features and prognosis. Methods We reviewed clinical, biological characteristics, diagnosis and management of 24 patients with anti-Ku antibody. A multidimensional analyze was performed to highlight homogeneous groups of patients. We search for features that most strongly match with each group. Results Anti-Ku positive patients had joint (n=19), muscle (n=10), lung (n=9), skin (n=9), renal (n=9), hematological (n=8), thrombotic (n=6), serous (n=6) and gastrointestinal (n=4) involvements. Associated antibodies were anti-DNA (n=7), -SSA (n=6), -RNP (n=4), -SSB (n=1), -Sm (n=1), rheumatoid factor (n=9) and ACPA (n=4). Diagnosis were overlap myositis (n=9), lupus erythematosus (n=8), Sjogren9s syndrome (n=7), rheumatoid arthritis (n=3), undifferentiated connective (n=2), and systemic sclerosis (n=2). Many patients had criteria for several connectivite tissue diseases. Managements were heterogeneous. Multidimensional analyze identified to groups that were mutually exclusive: (i) Patients characterized by scleroderma-like skin disease,myositis and ILD,frequently treated with high dose of corticosteroids, (ii) Patients with lupus like skin disease, haematological and renal involvements frequently receiving cyclophosphamide and mycophenolate mofetil. Anti-DNA antibody, absent in the first group and present in the second was the most powerful criteria to distinguish these two subsets of the anti-ku associated disease (sensibility 93% and a sensitivity of 86%). Conclusions Anti-DNA status distinguishes patients at risk of muscle and lung involvement (anti-DNA negative) from patients at risk of renal involvement (anti-DNA positive). These data significantly refine anti-Ku associated disease and help to personalize monitoring and care of the patients. Disclosure of Interest None declared

Fodrin, an actin binding protein found in the cytoskeleton of most eukaryotic cells, would seem to be an important organ-specific autoantigen in Sjogren’s syndrome (SS). Fodrin is, moreover, detected in the salivary glands of patients with primary SS (pSS) but not in controls. It was thus recently claimed that antibodies against α-fodrin are a sensitive and specific serological marker for pSS.1 In this study we investigated the prevalence of autoantibodies against α-fodrin in patients with pSS, as compared with healthy subjects and patients with other autoimmune diseases. The study group included 107 patients with well defined pSS (mean age 57.5 years), 32 patients with systemic lupus erythematosus (SLE; mean age 40.1 years), 43 patients with rheumatoid arthritis (RA; mean age 59.0 years) with no signs of secondary SS, and 48 healthy blood donors (mean age 84.3 years). A diagnosis of SLE, RA, or pSS was …

To investigate the prevalence of anti-cyclic citrullinated peptide (anti-CCP) and anti-keratin antibodies (AKA) in patients with primary Sjögren's syndrome.149 patients with a diagnosis of primary Sjögren's syndrome according to the European/American consensus criteria were recruited from three French medical centres. The presence of anti-CCP was determined by enzyme linked immunosorbent assay and of AKA antibodies by indirect immunofluorescence. Radiographs of hands and feet were evaluated at the time of anti-CCP analysis.Six patients with radiological erosions and nine patients with non-erosive arthritis fulfilling ACR criteria for rheumatoid arthritis were thought to have rheumatoid arthritis and secondary Sjögren's syndrome, while 134 were considered to have primary Sjögren's syndrome (mean (SD) disease duration, 11.1 (6.6) years). Of these, 80 tested positive for IgM rheumatoid factor (RF) (59%), 10 (7.5%) for anti-CCP, 7 (5.2%) for AKA, and 5 (3.7%) for both anti-CCP and AKA. There was no difference in clinical and biological features, including prevalence of RF, between anti-CCP positive and negative patients. The nine Sjögren patients with non-erosive arthritis, fulfilling ACR criteria for rheumatoid arthritis, were all CCP positive. Their response to disease modifying antirheumatic drugs could be different from classical rheumatoid patients.Most patients with primary Sjögren's syndrome are negative for AKA and anti-CCP, but positive test results should not rule out this diagnosis. Anti-CCP positive patients, who may be prone to developing rheumatoid arthritis, require cautious clinical and radiographic follow up.

Background: Anti-filaggrin antibodies (AFA) are among the most specific antibodies for rheumatoid arthritis, so procedures for their detection should be included in early biological diagnoses. AFA can be detected by indirect immunofluorescence (anti-keratin antibodies, AKA) or by new enzyme immunoassays (EIA). Their comparative performance needs to be established. Objective: To compare these technical procedures to optimise the serological diagnosis of rheumatoid arthritis. Methods: Results obtained using AKA and EIA were compared in 271 sera from 140 patients with rheumatoid arthritis at various stages, 98 patients with other autoimmune diseases, and 33 healthy subjects. EIA were successively undertaken with citrullinated linear filaggrin peptide (home made EIA) or cyclic citrullinated peptide (CCP2, commercial kits). Rheumatoid factor (RF) was assessed by EIA in all patients. Results: Anti-CCP2 kits showed the best sensitivity and specificity (65% and 96%, respectively). Among the 140 patients with rheumatoid arthritis, those with very recent disease (less than six months’ duration, n = 21) were studied as a separate group. In this group, the sensitivity of anti-CCP2 kits decreased to ~50%. Nevertheless this assay remained the most accurate when compared with AKA or home made EIA using linear filaggrin peptides. The combination of anti-CCP2 and RF only slightly increased the sensitivity of the diagnosis of very early rheumatoid arthritis. Conclusions: Kits using citrullinated cyclic peptides (CCP2) were more suitable than either AKA or EIA using linear filaggrin peptides for the diagnosis of early rheumatoid disease.