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Objective: Immunoglobulin G4-related disease (IgG4-RD) is a recently recognized heterogeneous, subacute, and usually silent autoimmune disease involving many organs with protean manifestations. However, high IgG4 in serum is not necessarily indicating an IgG4-RD. The aims of this study were to investigate the clinical relevance of high serum IgG4 level in IgG4-RD or non IgG4-RD patients, and to see if IgG4-RD in Taiwan differs from that in other parts of the world. Methods: Eight hundred forty-five patients with high IgG4 were retrospectively reviewed from January 2002 to May 2020 in Taipei Veteran General Hospital. Two hundred sixty-seven patients fulfilled IgG4-RD criteria and were categorized into pancreato-hepato-biliary disease, retroperitoneal fibrosis and/or aortitis, head/neck-limited disease, classic Mikulicz syndrome with systemic involvement, CNS-limited disease, sclerosing vasculitis, skin-limited disease, and sensorineural hearing disease. These manifestations were correlated to smoking, atopy, hyper-IgE/eosinophilia, aging, malignancies, and hypocomplementemia. Five hundred seventy-eight patients were not fulfilling the criteria but were also analyzed for the prevalence of allergy, malignancy, connective tissue diseases, lung diseases, and infections. Results: In IgG4-RD patients, 124 (46.4%) smoked. Top 4 clinical subtypes included Mikulicz syndrome with systemic involvement (33.3%), pancreato-hepatobiliary disease (31.4%), head/neck disease (19.4%), and retroperitoneal fibrosis/aortitis (12.7%). Top 4 co-morbid conditions included high serum IgE/eosinophilia (46.2%), hypocomplementemia (34%), malignancies (13.4%), and allergy (13.4%). Pancreato-biliary disease was associated with high IgE/eosinophilia (r2 = 0.380, P = 0.025) and malignancy (r2 = 0.211, P = 0.027), Miculicz syndrome with allergy (r2 = 0.396, P < 0.01) and high IgE/eosinophil (r2 = 0.396, P < 0.01), CNS diseases (r2 = 0.973, P = 0.035) and sclerosing vasculitis (r2 = 1, P < 0.01) with advanced age respectively, with the latter being also related to atopy and high IgE/eosinophilia (r2 = 1, p < 0.01). Conclusion: Smoking may precipitate IgG4-RD. IgG4-RD with pancreato-hepatobiliary disease is closely related to allergy and neoplasm, and those with Mikulicz syndrome may result from atopy. Elderly IgG4-RD patients tend to develop CNS pathology parallel to advancing of age. The disease may probably be originated from an unknown mechanism that may sporadically evolve into malignancies. [ABSTRACT FROM AUTHOR]

Treatment with biological disease-modifying anti-rheumatic drugs (bDMARDs) for rheumatoid arthritis (RA) and ankylosing spondylitis (AS) is popular. The aim of this study was to investigate changes in the quality of life (QoL) in patients after receiving, tapering, or stopping bDMARD treatment. Three hundred and thirty patients with RA and 120 patients with AS were enrolled. Data on the patients receiving bDMARDs were obtained by self-completed questionnaires including the short-form 36 (SF-36) and Global Quality of Life (GQL) scale. A relapse was defined as the QoL becoming worse than that before bDMARD treatment. Significant improvement in all domains of the SF-36 and GQL was noted in the patients after receiving bDMARDs. Improvement in SF-36 was significantly greater in RA patients with a shorter disease duration (< 6 years) and milder patient-assessed disease activity and in AS patients with a shorter disease duration and younger age. There were significant decreases in all domains of the SF-36 and GQL in both groups after reducing/discontinuing bDMARD treatment. The patients in both groups with a shorter period of bDMARD treatment (≤ 3 years) had significantly worse SF-36 scores compared to those with a longer period of bDMARD treatment (> 3 years). The relapse rate after reducing/discontinuing treatment was over 90.0% in the RA patients and over 50.0% in the AS patients within 12 months. bDMARDs significantly improved the QoL of the patients with RA and AS. However, interrupting or stopping the treatment protocol worsened the QoL and led to relapses, especially in the patients who used bDMARDs for a shorter period. [ABSTRACT FROM AUTHOR]

Background: Gremlin 1 (GREM1) is a bone morphogenetic protein antagonist and a novel proangiogenic factor. Our aim was to evaluate the prognostic value of GREM1 expression and GREM1-related factors in tumor-associated angiogenesis in pancreatic neuroendocrine tumors (NETs). Methods: The immunohistochemical expression of GREM1 and microvessel density (MVD) were examined in 35 patients with pancreatic NETs and then compared with other clinicopathologic characteristics, including the World Health Organization classification. Results: The presence of expression of GREM1 ( p = 0.016) and high MVD ( p = 0.020) were significant and favorable prognostic factors. Moreover, GREM1 expression was significantly associated with high MVD ( p = 0.011). MVD was significantly higher in well-differentiated NETs than in well-differentiated or poorly differentiated neuroendocrine carcinomas ( p < 0.001). Conclusions: GREM1 expression was correlated with tumor-associated angiogenesis and was found to be a novel prognostic marker in pancreatic NETS. Our data support a tumor suppressor role of GREM1 in pancreatic NETs. [ABSTRACT FROM AUTHOR]

The role of hepatitis B virus (HBV) infection in patients with primary Sjögren's syndrome (pSS) remains unclear. Therefore, we investigated the prevalence and clinical significance of HBV infection in Taiwanese patients with pSS. One hundred seventy-five patients with pSS who fulfilled the 2002 American-European Revised Classification Criteria were enrolled. Eighteen (10.3%) patients were positive for hepatitis B surface antigen (HBsAg). There were 4 males and 14 females, with the mean age of 54.4 years. The main immunological feature was rheumatoid factor (13 of 18, 72.2%), which was significantly higher than those negative for HBsAg (28.1%, p < 0.001). Twelve (66.7%) patients developed liver dysfunction, which was significantly different from the 15.3% of patients who were negative for HBsAg ( p < 0.001). There was no significant difference in extraglandular features between patients positive and negative for HBsAg, except patients positive for HBsAg had a lower rate to develop pulmonary involvement than those negative for HBsAg (5.6% vs. 29.9%, p = 0.027). The mortality rate of pSS patients positive for HBsAg during follow-up was 12.0% and the presence of HBV infection did not influence the survival rate ( p = 0.730). pSS patients with liver cirrhosis presented shorter median overall survival compared to those with without liver cirrhosis ( p < 0.001). Our findings suggest that HBV infection may protect individuals from pSS and reduce pulmonary involvement. [ABSTRACT FROM AUTHOR]

Programmed death 1 (PD-1) has been shown to be involved in the negative regulation of the immune response. However, the role of PD-1 in ankylosing spondylitis (AS) has not been studied. Therefore, we analyzed the expression of PD-1 in peripheral blood mononuclear cells (PBMC) from patients with AS. Twenty-three AS patients, 20 rheumatoid arthritis (RA) patients, and 25 normal healthy subjects were recruited. The percentage of the PBMC and PD-1 levels in these subjects were measured by flow cytometry. A higher percentage of CD4+ T cells was noted in AS patients than in healthy controls (37.53 ± 1.65% vs. 31.55 ± 0.92%, P < 0.01), but a similar result was not observed with regard to CD3+ T lymphocytes, CD4 + CD25 high + regulatory T cells, CD19+ B cells, and CD14+ and CD16+ monocytes/macrophages. PD-1 levels in PBMC were not significantly higher in AS patients than in RA patients or age- and gender-matched healthy controls and were also not correlated to the erythrocyte sedimentation rate, C-reactive protein, limitation of back flexion, and chest expansion in patients with AS. Of interest, the percentages of PD-1 + CD3+ T cells and PD-1 + CD4+ T cells were significantly lower in AS patients with higher modified Stokes Ankylosing Spondylitis Spinal Scores (mSASSS ≥30) than in those with lower mSASSS ( < 30; 0.07 ± 0.04% vs. 0.42 ± 0.14%, P < 0.05; 0.06 ± 0.03% vs. 0.40 ± 0.14%, P < 0.05, respectively). These results have suggested that the increased number of T helper cells lacking PD-1 may contribute to the spinal radiologic changes in AS patients. [ABSTRACT FROM AUTHOR]