Analyses of B cells in the bone marrow and secondary lymphoid tissues have revealed a broad range of cell surface markers defining B cell subpopulations, but only a few of these have been used to analyze B cell subpopulations in peripheral blood (PB). We report here the delineation of circulating PB B cell subpopulations by staining for CD19, CD38, and IgD in combination with CD10, CD44, CD77, CD95, CD23, IgM, and the B cell memory marker CD27. The utility of this approach is shown by the demonstration of disturbances of circulating B cell subpopulations in patients with autoimmune disease. Five mature B cell (Bm) subpopulations were identified in normal PB that were comparable with the tonsillar Bm1, Bm2, early Bm5, Bm5 subpopulations and, surprisingly, to the germinal center (GC) founder cell subpopulation (Bm2′ and Bm3δ–4δ), suggesting that some GC founder cells are circulating. No PB B cells resembled the Bm3 and Bm4 GC cells. Remarkably, some cells with the CD38−IgD+ phenotype, previously known as naive Bm1 cells, expressed CD27. The CD38−IgD+ subpopulation therefore includes both naive Bm1 cells and IgD+ memory B cells. This new classification of B cell developmental stages reveals disturbances in the proportions of B cell subpopulations in primary Sjögren’s syndrome (pSS) patients compared with healthy donors and rheumatoid arthritis patients. Patients with pSS contained a significantly higher percentage of B cells in two activated stages, which might reflect a disturbance in B cell trafficking and/or alteration in B cell differentiation. These findings could be of diagnostic significance for pSS.

We investigated the effects of acute starvation on mitogen-induced T-cell activation and Th1/Th2 cytokine responses in rheumatoid arthritis (RA) patients. Ten RA patients with active disease underwent a 7-day fast followed by a 2-week refeeding period. Immunological, hormonal, laboratory and clinical evaluations were carried out on days 0, 7 and 21. Using flow cytometry, mitogen-stimulated T-cell activation was assessed in fresh heparinised blood via analysis of CD69 expression. Production of Th1 (interferon-gamma) and Th2 (interleukin-4, IL-4) cytokines was also assessed by ELISA. The 7-day fast significantly decreased the erythrocyte sedimentation rate, C-reactive protein level, joint count, morning stiffness, body weight, CD4+ and CD8+ counts and CD69+ expression on mitogen stimulated CD4+ lymphocytes. A significant increase in mitogen-induced IL-4 production after fasting was found. The fast markedly reduced serum leptin and insulin-like growth factor-1 concentrations. No significant differences occurred in serum cortisol or prolactin before and after fasting. Decreases in CD4+ lymphocyte activation during fasting correlated with decreases in body weight. Our results suggest that the clinical and laboratory improvements in fasting RA patients may be attributed to decreased CD4+ T-cell activation and an increase in the number and/or function of IL-4-producing Th2 cells. Factors associated with loss of body weight during acute starvation appear to have an inhibitory effect on CD4+ lymphocyte activation.

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CD27 has been found to be expressed on somatically mutated B cells and is thus a positive marker for memory B cells in peripheral blood (PB). Since abnormal immunogloblin (Ig) production is characteristic of the autoimmune diseases primary Sjögren's syndrome (pSS) and rheumatoid arthritis (RA), we have analyzed in detail the CD27 expression on PB B cell from these patient groups. Staining of PB B cells with monoclonal antibodies (MoAb) specific for CD19 and CD27 revealed a significantly depressed percentage of CD27+ PB B cells in patients with pSS (14.8 ± 1.6%) compared to both healthy donors (31.3 ± 4.7%, P = 0.005) and patients with RA (40.8 ± 4.1%, P = 0.0001). In addition, the percentages of both the IgD+CD27+ and the IgD‐CD27+ B‐cell subpopulations were significantly lower in pSS patients compared to RA patients and healthy donors. However, the relative proportion of IgD‐ and IgD+ cells among the CD27+B cells were almost the same for the three groups. Our data suggest a disturbance in the differentiation of peripheral B cells and possibly a bias towards plasma cell differentiation, resulting in a depressed percentage of CD27+ memory PB B cells in pSS. These results are potentially of pathological significance and of diagnostic value.

In a 2-yr prospective follow-up study of patients presenting clinically with possible reactive arthritis (ReA), 17 (9%) of the patients turned out to have acute sarcoid arthritis (SA). The number of new cases of SA per year was 2.9/100,000 persons in the city of Oslo between 18 and 60 yr of age. The onset of SA clustered in the spring. All the SA patients presented with bilateral ankle joint involvement and bilateral hilar lymphadenopathy, and ten (59%) presented with the triad of erythema nodosum, arthritis and lung involvement. A prospective follow-up after 104 weeks showed complete remission of arthritis in all 17 cases of SA. The total duration of arthritis [median (range)] was 11 (2-107) weeks. Erythema nodosum was mild and transient in all cases. At week 104, the lung and hilar manifestations had resolved. We conclude that the outcome of SA appeared favourable. Bilateral ankle joint involvement, erythema nodosum and bilateral hilar lymphadenopathy found at the routine chest X-ray examination are important clues for the diagnosis of SA.

Hand radiography of 200 patients with rheumatoid arthritis RA was repeated after an interval of 12 months. Twenty joints including ten metacarpophalangeal joints, eight proximal interphalangeal joints and two interphalangeal joints of the thumbs were assessed. The number of joints with erosion was recorded, being referred to as Erosion Score. Additionally, each joint was graded on a zero to five point scale and the gradings of the individual joints were summed to form a score referred to as Damage Score. The progression in these scores during 12 months was recorded. The radiological joint damage was found to develop rapidly during the first years after disease onset and to assume a slow rate of increase after 9 years of the disease. The results imply that the disease duration is a critical feature for therapeutic studies. We suggest that patients with disease duration of less than 36 months only are suitable for therapeutic trials of RA and that the follow-up time should be at least 18 months if radiological assessment is used.

Fasting-associated increases in total plasma FFA concentrations do not inhibit, but rather enhance, in vitro lymphocyte proliferation. An inhibitory effect could only be achieved by manipulating the balance between the unsaturated and saturated fatty acids.

Objectives. Studies assessing relative mortality risks across the spectrum of systemic inflammatory rheumatic diseases are largely missing. In this study, we wanted to estimate standard mortality ratios (SMRs) and causes of death in an ethnically homogeneous cohort covering all major CTDs and primary systemic vasculitides (PSVs). Methods. We prospectively followed all incident CTD and PSV cases included in the Norwegian CTD and vasculitis registry (NOSVAR) between 1999 and 2015. Fifteen controls for each patient matched for sex and age were randomly drawn from the Norwegian National Population Registry. Causes of death were obtained from the National Cause of Death Register, death certificates and hospital charts.Results. The cohort included 2140 patients (1534 with CTD, 606 with PSV). During a mean follow-up time of 9 years, 279 of the patients (13%) died, compared with 2864 of 32 086 (9%) controls (P < 0.001). Ten years after diagnosis, the lowest survival was 60% in dcSSc, 73% in anti-synthetase syndrome (ASS) and 75% in lcSSc. In the CTD group, the highest SMRs were observed in dcSSc (SMR 5.8) and ASS (SMR 4.1). In the PSV group, Takayasu arteritis (SMR 2.5) and ANCAassociated vasculitis (SMR 1.5) had the highest SMRs. Major causes of death were cardiovascular disease (CTD 27%, PSV 28%), neoplasms (CTD 25%, PSV 27%), chronic respiratory disease (CTD 20%, PSV10%) and infections (CTD 9%, PSV 16%). Conclusion.We observed premature deaths across the spectrum of CTDs and PSVs, with highest SMRs in dcSSc and ASS. The overall mortality was highest in the CTD group.