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Objectives To investigate whether the auto-inflammatory nature and the pathergic reaction in Behçet's disease (BD) are driven by a disturbed toll-like receptor (TLR) response. Methods We compared both TLR expression by flow-cytometry and TLR response by stimulation assay in 18 BD patients (both pathergy positive and pathergy negative) with 15 healthy controls. Results Expression of TLR1 and 2 was significantly elevated in B-lymphocytes of BD patients compared with healthy controls. TLR1, 2 and 4 were significantly more highly expressed in both CD4+ and CD8+ T-lymphocytes of BD patients. Granulocytes of BD patients displayed significantly higher expression of TLR1, 2, 4 and 6. TLR2, 4 and 5 expression was significantly increased on classical monocytes of BD patients. Intermediate monocytes of BD patients showed an increase in expression of TLR2. Furthermore, TLR2 and 5 were significantly more highly expressed in non-classical monocytes of BD patients. In pathergy positive patients, TLR5 was even more highly expressed compared with pathergy negative patients on B- and T-lymphocytes and granulocytes. Furthermore, TLR2 and 5 showed an elevated TNF-α response to stimulation with their cognate ligands. Conclusion Immune cells of BD patients overexpress TLR1, 2, 4, 5 and 6. Furthermore, after stimulation of TLR2 and 5, BD patients demonstrate a more potent TNF-α response. Although this is a small cohort, in the pathergy positive patients, TLR5 expression is even further augmented, suggesting that a microbial (flagellin) or damage (HMGB1) associated signal may trigger the exaggerated immune response that is characteristic for the pathergy phenomenon in BD. In conclusion, these results point to an exaggerated TLR response in the auto-inflammatory nature of BD. [ABSTRACT FROM AUTHOR]

Objectives. Behçet's disease (BD), an auto-inflammatory vasculitis with oro-genital ulcerations, skin lesions and uveitis, is regarded as T cell mediated. A successful trial with rituximab suggests an additive role for B cells in the pathogenesis. Therefore, we studied B cell abnormalities in BD patients and the effect of TNF-blocking therapy. Methods. B cells in blood (n = 36) and tissue (n = 6) of BD patients were analysed with flow cytometry and/ or immunohistochemistry and compared with healthy controls (n = 22). BD current activity form (BDCAF) in relation to B cell somatic hypermutations (SHMs) and immunoglobulin class-switching were studied. Results. Thirty-six patients (17 males) were included, mean age 44 years, average disease duration 10 years and mean BDCAF 2.7. Blood B cell numbers were significantly lower in patients than in controls (P = 0.0061), mostly due to decreased CD27+ memory B cells expressing IgM (P = 0.0001), IgG (P = 0.0002) and IgA (P = 0.0038) B cell subsets. CD27+ IgA+ B cells showed the highest magnitude of decrease in active disease, measured with BDCAF (P = 0.02). CD27+ IgM+ IgD+ B cells were impaired in replication history (P = 0.0133) and selection of SHM, whereas IgA+ B cells carried elevated SHM levels (P = 0.04) and lower IgA2 subclass usage (P = 0.0004) than controls. Immunohistochemistry revealed B cells in tissue of active mucosal ulcers. In adalimumab-treated patients, blood B cells were similar to controls. Conclusion. We show significant deviations in the memory B cell compartment, related to disease activity and therapeutic efficacy. Pronounced molecular impairments were seen in the fast-responding IgM+-memory and the mucosal IgA+-memory B cells. Because of the demonstrated abundance of B cells in affected tissue, we hypothesize relocation of memory B cells to the site of inflammation could account for the deviations found in blood of BD patients. These peripheral B cells are easily accessible as a marker to monitor therapeutic efficacy. [ABSTRACT FROM AUTHOR]

The article presents cases of IgG4-related disease (RD) that were initially suspected of limited granulomatosis with polyangiitis (GPA). Topics discussed include challenges of IgG4-RD diagnosis, importance of correct histological assessment of IgG4-RD, and consequence of prolonged untreated inflammation due to IgG4-RD.

Objectives. Our objectives were to analyse the prevalence of distal renal tubular acidosis (dRTA) in primary SS (pSS) and to compare a novel urinary acidification test with furosemide and fludrocortisone (FF) with the gold standard ammonium chloride (NH4Cl) to detect dRTA. Methods. Urinary acidification was assessed in 57 pSS patients using NH4Cl and FF. A urinary acidification defect was defined as an inability to reach a urinary pH of <5.3 after NH4Cl. Results. The prevalence of complete dRTA (urinary acidification defect with acidosis) was 5% (3/57). All three patients had positive SSA/Ro and SSB/La autoantibodies and impaired kidney function. The prevalence of incomplete dRTA (urinary acidification defect without acidosis) was 25% (14/57). Compared with patients without dRTA, patients with incomplete dRTA had significantly lower venous pH and serum bicarbonate and higher urinary pH. SSB/La antibodies were more prevalent in the dRTA groups (P < 0.05). Compared with NH4Cl, the positive and negative predictive values of FF were 46% and 82%, respectively. Vomiting occurred more often during the urinary acidification test with NH4Cl than with FF (9 vs 0, P < 0.05). Conclusion. Incomplete dRTA is common in pSS and causes mild acidaemia and higher urinary pH, which may contribute to bone demineralization and kidney stone formation. FF cannot replace NH4Cl in testing urinary acidification in pSS, but may be considered as a screening tool, given its reasonable negative predictive value and better tolerability. [ABSTRACT FROM AUTHOR]

The article discusses research which examined the applicability of myxovirus resistance protein 1 (MxA) enzyme immunoassay (EIA) in detecting type I interferon (IFN) activation in individuals with systemic lupus erythematosus (SLE) and systemic sclerosis (SSc). Topics explored include the measurement of MxA protein levels in patients with SLE, observations on the IFN scores and autoantibodies of SLE patients, and the cost-effectiveness demonstrated by MxA-EIA.

The author comments on the article "Exploring the variability in Behc¸et's Disease Prevalence: A Meta-Analytical Approach" by Carla Maldini et al. He explores the origin of Behc¸et's disease, a multisystem auto-inflammatory disorder named after Turkish dermatologist Hulusi Behc¸et. He explains the rarity of the disease and its potential environmental of genetic causes, as well as its immunological mechanistic pathways.

A letter to the editor is presented in response to the article "Hemophagocytic lymphohistiocytosis associated with Bartonella henselae infection in an HIV-infected patient," by A. Le Joncour and colleagues in a 2016 issue.