IL-10 producing Bregs are impaired in psoriatic arthritis and psoriasis and inversely correlate with IL-17- and IFNγ-producing T cells.

Our aim was to study CD19(+)CD27(+)CD24(high) memory and CD19(+)CD24(high)CD38(high) transitional and IL-10+Breg cells, known to inhibit Th1 and Th17 cells in experimental arthritis, in psoriatic arthritis (PsA) and psoriasis (Ps). Peripheral blood Breg cells from 60 patients with PsA, 50 patients with Ps and 23 healthy controls were analyzed by flow cytometry. IL-17A-producing CD3(+) T cells and IFNγ-producing CD3(+) T cells and activation of p38 MAPK and STAT3 were also studied. CD19(+)CD27(+)CD24(high) and CD19(+)CD24(high)CD38(high) Breg cells were decreased in PsA and Ps. In Ps patients, CD19(+)CD27(+)CD24(high) Breg cells inversely correlated with PASI score. IL-10+Bcells were also decreased and inversely correlated with IL-17A+CD3+ and IFN-γ+CD3+ T cells. B cells from patients exhibited impaired activation of p38 MAPK and STAT3. In conclusion, IL-10+Breg cells are decreased PsA and Ps and inversely correlated with the severity of psoriasis and IL-17A+ and IFNγ+ T cells.

Anti-MCV antibodies predict radiographic progression in Greek patients with very early (<3 months duration) rheumatoid arthritis.

This study aimed to assess the diagnostic and prognostic value of anti-mutated citrullinated vimentin (MCV) antibodies in very early rheumatoid arthritis (VERA) and in established rheumatoid arthritis (RA). Seventy-one patients with undifferentiated arthritis (UA) of <3 months duration, 141 with established RA, 53 with other rheumatic diseases, and 40 healthy individuals were included in the study. Anti-MCV, anti-cyclic citrullinated peptide (CCP) antibodies, and rheumatoid factor (RF) were determined and hand radiographs were recorded. Patients were assessed prospectively for 2 years, and hand radiographs were repeated. Diagnostic performance of anti-MCV was studied with receiver operating characteristic (ROC) curves and evaluation of sensitivity, specificity, and likelihood ratios. Forty-six percent of UA patients progressed to RA at 2 years. In VERA patients, sensitivity of anti-MCV was 52 %, compared to 44 % of anti-CCP and 37 % of RF, while specificity was 91 %, compared to 91 % of RF and 84 % of anti-CCP. Anti-MCV were detected in 25 % of VERA patients negative for both anti-CCP and RF. In established RA, anti-MCV did not sustain its diagnostic performance. By multivariable analysis, anti-MCV, but not anti-CCP or RF, showed significant correlation with radiographic progression in VERA patients. In established RA, anti-MCV, anti-CCP, and RF were associated with active disease (p ≤ 0.03) and joint damage (p ≤ 0.004). By multivariate analysis, the strongest factors for radiographic damage were disease duration (p = 0.000), HAQ score (p = 0.000), and RF (p = 0.002). In conclusion, in patients with very early UA, anti-MCV predict both progression to RA and radiological damage, and therefore, anti-MCV antibody testing may be useful in every day practice.

Breg Cells Are Numerically Decreased and Functionally Impaired in Patients With Systemic Sclerosis.

OBJECTIVE: Breg cells, a regulatory cell subset that produces interleukin-10 (IL-10), play a significant role in suppressing autoimmune responses and preventing autoimmunity. This study was undertaken to examine the number and function of Breg cells in patients with systemic sclerosis (SSc), a disease with many autoantibodies. METHODS: Forty-five patients with SSc (12 with early SSc, 33 with established disease including 16 with SSc-associated pulmonary fibrosis [PF]), 12 healthy control subjects, and 10 patients with rheumatoid arthritis (RA)-associated PF were studied. The phenotypes of immature/transitional Breg cells (CD19+CD24(high) CD38(high) ) and memory Breg cells (CD19+CD27+CD24(high) ) were evaluated by flow cytometry. The function of Breg cells was assessed by measuring the production of IL-10 after B cell activation. In addition, activation of p38 MAPK and STAT-3 was measured following stimulation of the cells with B cell receptor (BCR) and Toll-like receptor 9 (TLR-9). RESULTS: Percentages of memory Breg cells were decreased in patients with early SSc (mean ± SEM 1.85 ± 0.38%), those with established SSc (1.6 ± 0.88%), those with SSc-associated PF (1.52 ± 0.17%), and those with RA-associated PF (1.58 ± 0.26%), compared to healthy controls (6.3 ± 0.49%; each P < 0.001). Percentages of transitional Breg cells were also decreased. Expression of IL-10 by Breg cells after stimulation with TLR-9 was impaired in patients with SSc, particularly those with SSc-associated PF. Activation of STAT-3 and p38 MAPK was impaired in naive and memory B cells from patients with SSc after stimulation with BCR and TLR-9. Expression of the stimulatory CD19 receptor was increased in B cells and also increased, to a lesser extent, in Breg cells from patients with SSc compared to healthy controls. Percentages of memory B cells were decreased in patients with SSc, particularly in those with SSc-associated PF. CONCLUSION: This is the first study to demonstrate that Breg cells are phenotypically and functionally impaired in patients with SSc. Furthermore, in SSc, B cells exhibit impaired p38 MAPK and STAT-3 activation upon stimulation with BCR and TLR-9. The findings of decreased numbers of Breg cells along with increased expression of CD19 support the idea of B cell autoaggression acting as an immunopathogenic mediator in SSc.

Tuberculous pyomyositis: a re-emerging entity of many faces.

Tuberculosis (TB) has become a global concern due to its increasing incidence, particularly in immunocompromised patients, closely following the migratory patterns of populations. TB pyomyositis is a rare extrapulmonary manifestation of TB. Its clinical presentation varies and requires a high degree of suspicion for early diagnosis. We present three patients diagnosed with TB pyomyositis: a 46-year-old man with dermatomyositis (DM) and hepatitis B who presented with fever, muscle weakness, and an abscess at the right proximal arm; a 71-year-old immunocompetent male, with a past medical history of tuberculous lymphadenopathy in childhood, who presented with a 2-month history of fever and pain at the right thigh, and a 44-year-old woman with systemic lupus erythematosus (SLE) on prednisone and methotrexate who presented with skin eruption at her thighs mimicking lupus panniculitis. In all three patients, Mycobacterium tuberculosis was identified as the causative agent. The lack of specific signs, the false negative tuberculin skin test in some cases, and the unfamiliarity of many clinicians with this entity can cause diagnostic delays. Prompt diagnosis requires a high index of suspicion especially in immunocompromised patients with fever.