Anti-SSA/SSB-negative primary Sjögren's syndrome showing different clinical phenotypes: a retrospective study of 934 cases

Abstract Background Currently, only a few studies have described the general characteristics of patients with primary Sjögren's syndrome (pSS) who tested negatives for anti-SSA and anti-SSB antibodies. We aimed to further investigate the clinical characteristics of these patients in a large sample. Methods Data from patients with pSS who were treated at a tertiary hospital in China between 2013 and 2022 were retrospectively analyzed. Clinical characteristics of the patients were compared between those with and without anti-SSA and anti-SSB antibody negativity. Factors associated with anti-SSA and anti-SSB negativity were identified by logistic regression analysis. Results Overall, 934 patients with pSS were included in this study, among whom 299 (32.0%) tested negative for anti-SSA and anti-SSB antibodies. Compared with patients testing positive for anti-SSA or anti-SSB antibodies, that testing negative for the two antibodies had a lower proportion of females (75.3% vs. 90.6%, p < 0.001) and thrombocytopenia (6.7% vs. 13.6%, p = 0.002), but a higher proportion of abnormal Schirmer I tests (96.0% vs. 89.1%, p = 0.001) and interstitial lung disease (ILD) (59.2% vs. 28.8%, p = 0.001). Anti-SSA and anti-SSB negativity was positively associated with male sex (odds ratio [OR] = 1.86, 95% confidence interval [CI]: 1.05, 3.31), abnormal Schirmer I tests (OR = 2.85, 95% CI: 1.24, 6.53), and ILD (OR = 2.54, 95% CI: 1.67, 3.85). However, it was negatively related to thrombocytopenia (OR = 0.47, 95% CI: 0.24, 0.95). Conclusion Approximately one third of pSS patients had anti-SSA and anti-SSB negativity. pSS patients testing negative for anti-SSA and anti-SSB showed a higher risk of abnormal Schirmer I tests and ILD, but a lower risk of thrombocytopenia.

Differential Regulation of Integrin α5 and ß4 in Normal and Psoriatic Epidermal Keratinocytes

Abstract Psoriasis is a chronic skin inflammation, characterized by impaired differentiation, hyperproliferation of keratinocytes involving pro-inflammatory factors interleukin (IL)-13/17A, tumor necrosis factor (TNF)-α, interferon (IFN)-γ. Among the integrin family, α5 is important for blood vessel formation, and ß4 for proliferation, differentiation of keratinocytes. To investigate the expression and regulation of integrin α5 and ß4 in psoriatic keratinocytes. Skin biopsies were obtained from 14 psoriatic patients and 12 normal volunteers. We compared the immunolocalization and regulation of α5 and ß4 between the psoriatic and normal ones, before and after incubation with MEK/ERK pathway inhibitor U0126 by immunohistochemistry and western blot separately. Immunohistochemistry showed psoriatic keratinocytes had higher α5 than normal ones. According to western blot, IL-17A and IL-13 increased normal keratinocytes' α5 and ß4 respectively, but psoriatic keratinocytes were the exact opposite. Incubated with U0126, normal keratinocytes' α5 was enhanced by the 5 cytokines ; while IL-13/17A, IFN-γ suppressed ß4. Psoriatic keratinocytes' α5 was increased by IL-13/17A, decreased by IFN-γ; but ß4 increased by IL-17A, IFN-γ. IL-13/17A, TNF-α, IFN-γ regulate α5 and ß4 through ERK pathway whether normal or psoriasis. The normal and psoriatic keratinocytes respond to the same cytokines differently

Synthesis of multi-substituted pyridines from ylidenemalononitriles and their emission properties.

Numerous methodologies to obtain pyridines from ylidenemalononitriles are described in the literature. Nevertheless, they are limited to the use of microwave or conventional heat and few lead to 2,3,4 or 2,3,4,5-substituted pyridines as multi-proposal molecular scaffolds or even universal pyridines. Herein, we present a mild and facile solvent-free methodology to obtain a scope of multi-substituted pyridines at room temperature. We also report an example where one of the resulting amino-nicotinonitriles exhibits a preliminary evidence of aggregation-induced emission (AIE).