BackgroundFavorable treatment outcomes with TNF blockade led us to explore cytokine responses in hidradenitis suppurativa (HS).MethodsBlood monocytes of 120 patients and 24 healthy volunteers were subtyped by flow cytometry. Isolated blood mononuclear cells (PBMCs) were stimulated for cytokine production; this was repeated in 13 severe patients during treatment with etanercept. Cytokines in pus were measured.ResultsCD14brightCD16dim inflammatory monocytes and patrolling monocytes were increased in Hurley III patients. Cytokine production by stimulated PBMCs was low compared to controls but the cytokine gene copies did not differ, indicating post-translational inhibition. The low production of IL-17 was restored, when cells were incubated with adalimumab. In pus, high concentrations of pro-inflammatory cytokines were detected. Based on the patterns, six different cytokine profiles were discerned, which are potentially relevant for the choice of treatment. Clinical improvement with etanercept was predicted by increased production of IL-1β and IL-17 by PBMCs at week 8.ConclusionsFindings indicate compartmentalized cytokine expression in HS; high in pus but suppressed in PBMCs. This is modulated through blockade of TNF.

Objectives: Autoimmune antibody profiling plays a prominent role in both classification and prognosis of systemic sclerosis (SSc). In the last years novel autoantibodies have been discovered and have become available in diagnostic assays. However, standardization in autoimmune serology is lacking, which may have a negative impact on the added value of autoantibodies in diagnosis and prognosis of SSc. In this paper we describe the comparison of commercially available diagnostic assays for the detection of SSc-associated autoantibodies and explored the coexistence of multiple SSc-associated autoantibodies within patients. Methods: Serum samples of 347 patients from the Nijmegen Systemic Sclerosis Cohort were included in this study. All patients fulfilled the ACR/EULAR 2013 classification criteria for SSc and were classified as DcSSc or LcSSc according to the Leroy and Medsger criteria. All samples were evaluated on standard laboratory diagnostic tests for detection of SSc-specific autoantibodies CENPA and CENPB (ACA), Scl-70 (ATA), RNA Polymerase III (rp11/155) (ARA), and SSc-associated autoantibodies Fibrillarin, Th-To, PM-scl75, PM-Scl100, RNP68/A/C, Ku, NOR90, and PDGFR from suppliers EUROIMMUN, D-tek and Thermo Fisher Scientific. Results: We found that 79% of the patients was positive for one or more of the SSc autoantibodies. Overall, a high agreement was observed between the diagnostic methods for the SSC-specific autoantibodies listed in the ACR/EULAR criteria (ATA, ACA, and ARA) (Cohen's kappa 0.53-0.97). However, a lower agreement was found for SSc-associated autoantibodies PM-Scl, and Ku, as well as for the SScspecific autoantibodies fibrillarin and Th-To. Furthermore, the data revealed that the presence of ATA, ARA and ACA is predominantly mutually exclusive, with only a fraction of the patients testing positive for both ATA and ARA. Conclusion: Our data showed high concordance of prevalent SSc-specific autoantibodies between different diagnostic assays. Further standardisation for low prevalent SSc-specific and SSc-associated autoantibodies is needed.

Introduction Systemic sclerosis starts with an early phase characterized by Raynaud’s phenomenon, puffy fingers/hands, autoantibodies, and a scleroderma nailfold microscopic pattern. Alterations in the nailfold microscopic pattern are not evident in all early SSc patients. Photoacoustics (PA) and high-frequency ultrasound (HFUS) could fulfill this need. The former can measure oxygen saturation while the latter can measure skin thickening. We hypothesize that photoacoustics and high-frequency ultrasound can distinguish (early) SSc patients from individuals with primary Raynaud’s phenomenon (PRP) by measuring oxygenation of the fingertip and skin thickening. Methods We compared measurements of oxygenation and skin thickness of the third finger between (early) SSc patients and PRP individuals and healthy controls. The spearman rank correlation was used to analyze an association between capillary density and oxygen saturation of the fingers. Results Thirty-one adult subjects participated in this study: twelve patients with SSc, 5 patients with early SSc, 5 volunteers with PR, and 9 healthy controls. We found a significant difference in oxygen saturation between (early) SSc patients (80.8% ± 8.1 and 77.9% ± 10.5) and individuals with PRP (93.9% ± 1.1). Measurements of skin thickening showed a significant difference in (early) SSc patients compared to individuals with PRP (0.48 ± 0.06 mm and 0.51 ± 0.16 mm vs. 0.27 ± 0.01 mm). There was no significant difference between healthy and PRP individuals in oxygenation or skin thickening. Conclusion Photoacoustic and high-frequency ultrasound could help to distinguish between (early) SSc, PRP, and healthy individuals in both oxygenation and skin thickening.

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