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Objective: SSc is a connective tissue disease with multisystem disorder induced by the inflammation and fibrosis following T and B cell abnormalities. Follicular helper CD4+ T (TFH) cells play a crucial role in the formation of germinal centres and specialize in interacting to aid B cell differentiation. We aimed to investigate TFH cells and their subsets to evaluate their involvement with B cell alteration in SSc., Method: Circulating TFH cells (cTFH), B cells and their subsets were assessed by flow cytometry. The concentration of serum cytokines was measured by cytokine array assay. Immunohistochemistry and IF were performed to evaluate the migration of TFH cells in SSc skin lesions., Results: The proportion of cTFH cells did not differ from controls, but their subsets were imbalanced in SSc patients. The frequency of TFH 1 was increased and correlated with ACA titre, serum IgM or CRP levels of patients, and cytokine concentrations of IL-21 and IL-6 that induce B cell differentiation in SSc. cTFH cells from SSc showed activated phenotype with expressing higher cytokine levels compared with controls. The frequency of TFH 17 was also increased, but was not correlated with a high level of Th17 cytokines in patients' sera. Furthermore, infiltration of TFH cells was found in skin lesion of SSc patients., Conclusion: We here describe an imbalance of cTFH toward TFH 1 that may induce B cell alteration through IL-21 and IL-6 pathways and promote inflammation, contributing to the pathogenesis of SSc disease., (© The Author(s) 2020. Published by Oxford University Press on behalf of the British Society for Rheumatology. All rights reserved. For permissions, please email: journals.permissions@oup.com.)

Background: Myositis-specific autoantibodies (MSAs) are associated with unique clinical subsets in polymyositis/dermatomyositis (PM/DM). Autoantibodies against transcriptional intermediary factor (TIF)-1γ and TIF-1α are known to be MSAs. Previously, we reported that TIF-1β is also targeted in patients with DM with or without concomitant anti-TIF-1α/γ antibodies., Objectives: To evaluate the clinical features of seven cases with anti-TIF-1β antibodies alone., Methods: Serum autoantibody profiles were determined, and protein and RNA immunoprecipitation studies were conducted. Western blotting was performed to confirm autoantibody reactivity against TIF-1β., Results: Anti-TIF-1β antibody was identified by immunoprecipitation assay in 24 cases. Among them, seven patients were positive for anti-TIF-1β antibody alone. Six of the seven patients were classified as having DM. Among the six cases of DM, two patients had no muscle weakness and normal creatine kinase (CK) levels, and were classified as having clinically amyopathic DM. Four patients had muscle weakness, but three of them had normal serum CK levels that responded well to systemic steroids. Characteristic features of DM included skin rashes, such as Gottron sign, periungual erythema, punctate haemorrhage on the perionychium and facial erythema including heliotrope, which were observed in 86%, 57%, 86% and 71% of our cases, respectively. One of the seven patients had appendiceal cancer. None of the patients had interstitial lung disease., Conclusions: Seven patients were confirmed to have anti-TIF-1β antibody without any other MSAs, including TIF-1α/γ antibodies, and six of them were diagnosed with DM. We suggest that anti-TIF-1β antibody is an MSA, and that it is associated with clinically amyopathic DM or DM with mild myopathy., (© 2018 British Association of Dermatologists.)

Systemic sclerosis (SSc)-related autoantibodies are useful tools in identifying clinically homogenous subsets of patients and predicting their prognosis. In this report, we described five SSc patients with anti-centriole antibodies. All five patients were females and had digital ulcers/gangrene. Four of five (80%) patients had pulmonary arterial hypertension (PAH). None of the five patients had active pulmonary fibrosis or developed renal crisis. Anti-centriole antibodies may be a marker for PAH and digital ulcers/gangrene.

Objective: The purpose of this study was to determine serum levels of B-cell-activating factor (BAFF) and its clinical association in patients with sarcoidosis. METHODS; Serum levels of BAFF from 37 patients and 21 healthy subjects were examined by ELISA. Serum angiotensin-converting enzyme (ACE), lysozyme and IFN-γ levels in sarcoidosis patients were also measured. Isolated monocytes cultured with IFN-γ, IL-4 or IL-10 and their expression of membrane and soluble BAFF were analysed by flow cytometry or ELISA. Peripheral B cell subsets were analysed by flow cytometry. BAFF expression in the granuloma of the skin was examined by immunohistochemistry. ANAs were determined by indirect IF using HEp-2 cells as a substrate., Results: Serum BAFF levels were significantly elevated in sarcoidosis patients when compared with healthy controls. The frequency of skin and eye involvement was significantly higher in patients with elevated serum BAFF than in patients with normal levels. Serum BAFF levels were correlated with serum levels of ACE, lysozyme and IFN-γ. Immunostaining of anti-BAFF in the skin revealed BAFF expression by epithelioid cells of granuloma. In vitro, IFN-γ induced membrane-bound BAFF expression on monocytes and secretion of soluble BAFF by isolated monocytes. In the peripheral blood, sarcoidosis patients showed increased naïve B cells with a reciprocal decrease in memory B cells and plasmablasts. Seventeen of 26 (65%) sarcoidosis patients exhibited ANA positivity., Conclusion: Serum BAFF levels can be used as a surrogate marker of disease activity in sarcoidosis patients. Increased BAFF may be related to the pathogenesis of sarcoidosis.

Objectives: The purpose of this study was to determine the prevalence of anti-CCP antibodies (anti-CCP Abs) and to assess associations between the presence of anti-CCP Ab and arthritis or arthralgia in SSc patients., Methods: Serum samples were obtained from 146 SSc patients. Anti-CCP Ab, anti-agalactosyl (AG) IgG Ab, IgM-RF, IgG-RF and MMP-3 were determined, respectively., Results: The presence of anti-CCP Ab was found in 18/146 (12%) patients with SSc. Elevated levels of anti-AG IgG Abs, IgM- and IgG-RFs were observed in 50/146 (34%), 17/146 (12%) and 4/146 (3%), respectively. Serum anti-CCP Ab levels were significantly elevated in SSc-RA overlap patients compared with SSc patients with or without arthralgia (P < 0.05 or P < 0.001, respectively). Serum MMP-3 levels did not correlate with the presence of arthritis or arthralgia but were significantly associated with modified Rodnan total skin thickness score. In SSc-RA overlap patients, 10/11 (91%) patients were positive for two or more RA-related Abs., Conclusions: The serum titre of anti-CCP Ab is higher in SSc-RA overlap patients than in SSc patients with or without arthralgia. The finding of high titres of anti-CCP Abs and the elevated levels combinatory with other RA-related Abs may help to define the diagnosis of SSc-RA overlap. MMP-3 might be a better marker to assess skin involvement rather than joint involvement in SSc patients.

Objective: To assess red blood cell velocity in finger nail-fold capillaries using video capillaroscopy in patients with SSc and other collagen diseases., Methods: This study included 127 patients with SSc as well as patients with SLE (n = 33), DM/PM (n = 21), RA (n = 13) and APS (n = 12), and 20 healthy subjects. Red blood cell velocity was evaluated using frame-to-frame determination of the position of capillary plasma gaps., Results: The mean red blood cell velocity was significantly decreased in patients with SSc compared to healthy controls (63.0% reduction) and patients with other conditions. Mean blood velocity was similar between patients with dcSSc and lcSSc. Importantly, even SSc patients with normal or non-specific nail-fold video capillaroscopic (NVC) patterns or a scleroderma early NVC pattern exhibited a significantly lower red blood cell velocity compared to healthy controls (51.7 and 61.4% reduction, respectively) or patients with other conditions, despite normal or mild capillary changes. Patients with the scleroderma active and late NVC pattern showed a more decreased blood velocity (65.5 and 66.2% reduction, respectively). This reduced blood velocity was significantly associated with NVC findings, including capillary ramification and capillary loss. Although remarkably reduced velocity was observed in SSc patients with intractable digital ulcers (72.1% reduction), it was significantly improved by lipo-prostaglandin E(1) (lipo-PGE(1)) infusion., Conclusion: Our results suggest that reduced blood velocity is a hallmark of SSc. Furthermore, measurement of red blood cell velocity may be useful in evaluating therapeutic effects on microcirculation.