Hydrogen sulfide as potential regulatory gasotransmitter in arthritic diseases

The social and economic impact of chronic inflammatory diseases, such as arthritis, explains the growing interest of the research in this field. The antioxidant and anti-inflammatory properties of the endogenous gasotransmitter hydrogen sulfide (H2S) were recently demonstrated in the context of different inflammatory diseases. In particular, H2S is able to suppress the production of pro-inflammatory mediations by lymphocytes and innate immunity cells. Considering these biological effects of H2S, a potential role in the treatment of inflammatory arthritis, such as rheumatoid arthritis (RA), can be postulated. However, despite the growing interest in H2S, more evidence is needed to understand the pathophysiology and the potential of H2S as a therapeutic agent. Within this review, we provide an overview on H2S biological effects, on its role in immune-mediated inflammatory diseases, on H2S releasing drugs, and on systems of tissue repair and regeneration that are currently under investigation for potential therapeutic applications in arthritic diseases

Autoantibodies in inflammatory arthritis

Rheumatoid arthritis (RA) is a systemic chronic inflammatory disease characterized by extensive synovitis resulting in erosions of articular cartilage and marginal bone with joint destruction. The lack of immunological tolerance in RA represents the first step toward the development of autoimmunity. Susceptible individuals, under the influence of environmental factors, such as tobacco smoke, and silica exposure, develop autoimmune phenomena that result in the presence of autoantibodies. HLA and non-HLA haplotypes play a major role in determining the development of specific autoantibodies differentiating anti-citrullinated antibodies (ACPA)-positive and negative RA patients. Rheumatoid factor (RF) and ACPA are the serological markers for RA, and during the preclinical immunological phase, autoantibody titers increase with a progressive spread of ACPA antigens repertoire. The presence of ACPA represents an independent risk factor for developing RA in patients with undifferentiated arthritis or arthralgia. Moreover, anti-CarP antibodies have been identified in patients with RA as well as in individuals before the onset of clinical symptoms of RA. Several autoantibodies mainly targeting post-translational modified proteins have been investigated as possible biomarkers to improve the early diagnosis, prognosis and response to therapy in RA patients. Psoriatic arthritis (PsA) is distinguished from RA by infrequent positivity for RF and ACPA, together with other distinctive clinical features. Actually, specific autoantibodies have not been described. Recently, anti-CarP antibodies have been reported in sera from PsA patients with active disease. Further investigations on autoantibodies showing high specificity and sensibility as well as relevant correlation with disease severity, progression, and response to therapy are awaited in inflammatory arthritides

Interrogation of the perturbed gut microbiota in gouty arthritis patients through in silico metabolic modeling

Recent studies have shown perturbed gut microbiota associated with gouty arthritis, a metabolic disease characterized by an imbalance between uric acid production and excretion. To mechanistically investigate altered microbiota metabolism associated with gout disease, 16S rRNA gene amplicon sequence data from stool samples of gout patients and healthy controls were computationally analyzed through bacterial community metabolic models. Patient-specific community models constructed with the metagenomics modeling pipeline, mgPipe, were used to perform k-means clustering of samples according to their metabolic capabilities. The clustering analysis generated statistically significant partitioning of samples into a Bacteroides-dominated, high gout cluster and a Faecalibacterium-elevated, low gout cluster. The high gout cluster was predicted to allow elevated synthesis of the amino acids D-alanine and L-alanine and byproducts of branched-chain amino acid catabolism, while the low gout cluster allowed higher production of butyrate, the sulfur-containing amino acids L-cysteine and L-methionine, and the L-cysteine catabolic product H2S. By expanding the capabilities of mgPipe to provide taxa-level resolution of metabolite exchange rates, acetate, D-lactate and succinate exchanged from Bacteroides to Faecalibacterium were predicted to enhance butyrate production in the low gout cluster. Model predictions suggested that sulfur-containing amino acid metabolism generally and H2S more specifically could be novel gout disease markers

SARS-CoV-2-specific immune responses and clinical outcomes after COVID-19 vaccination in patients with immune-suppressive disease

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) immune responses and infection outcomes were evaluated in 2,686 patients with varying immune-suppressive disease states after administration of two Coronavirus Disease 2019 (COVID-19) vaccines. Overall, 255 of 2,204 (12%) patients failed to develop anti-spike antibodies, with an additional 600 of 2,204 (27%) patients generating low levels (<380 AU ml−1). Vaccine failure rates were highest in ANCA-associated vasculitis on rituximab (21/29, 72%), hemodialysis on immunosuppressive therapy (6/30, 20%) and solid organ transplant recipients (20/81, 25% and 141/458, 31%). SARS-CoV-2-specific T cell responses were detected in 513 of 580 (88%) patients, with lower T cell magnitude or proportion in hemodialysis, allogeneic hematopoietic stem cell transplantation and liver transplant recipients (versus healthy controls). Humoral responses against Omicron (BA.1) were reduced, although cross-reactive T cell responses were sustained in all participants for whom these data were available. BNT162b2 was associated with higher antibody but lower cellular responses compared to ChAdOx1 nCoV-19 vaccination. We report 474 SARS-CoV-2 infection episodes, including 48 individuals with hospitalization or death from COVID-19. Decreased magnitude of both the serological and the T cell response was associated with severe COVID-19. Overall, we identified clinical phenotypes that may benefit from targeted COVID-19 therapeutic strategies

Clinical and radiological signs of ABPA associated with airways infection wlth Aspergillus in the absence of specific IgE

Allergic bronchopulmonary aspergillosis (ABPA) is a hypersensitivity reaction to Aspergillus that mainly affects patients with asthma. For diagnosis, elevated serum IgE level are needed according to Greenberger and Patterson criteria. We report a case of 43 years-old woman who developed ABPA with productive cough, fever and radiological findings of multiple confluent areas of consolidation in both upper lobes. Laboratory tests showed elevated peripheral eosinophil counts (9.3 x 10(3)/ml). In bronchial washing A. galactomannans and A. Fumigatus were isolated, although we found normal levels of serum IgE, and the absence of serum IgG and IgE antibodies to Aspergillus and A. galactomannans. In conclusion, clinical and radiological signs of ABPA can be associated with Aspergillus infection also in the absence of a specific serum antibody reaction

Remission and low disease activity in a cohort of real-life patients with rheumatoid arthritis treated with first-line antitumour necrosis factor

Objectives: This retrospective study used various indices to evaluate remission and low disease activity in ‘real life’ patients with rheumatoid arthritis (RA), given antitumour necrosis factor (anti-TNF) as a first-line treatment; changes in concomitant steroid and conventional synthetic disease-modifying antirheumatic drug (csDMARD) treatment were also assessed. Methods: Remission and low disease activity were analysed in patients with RA treated with anti-TNF using the 28-joint Disease Activity Score (DAS28), Simplified Disease Activity Index (SDAI) and Clinical Disease Activity Index (CDAI). Remission and low disease activity were recorded after 6 months, 1 year and 2 years, along with concomitant prednisone and csDMARD treatment. Results: A total of 271 patients with RA were included in the study. After 6 months, remission rates were 18.0%, 20.3% and 23.0% as assessed by CDAI, SDAI and DAS28, respectively. After 1 year and 2 years, respectively, remission rates were 18.4% and 15.9% using CDAI, 21.8% and 17.3% using SDAI, and 22.1% and 17.3% using DAS28. Low disease activity was achieved in 30–40% of patients, depending on the indices used. There was a significant reduction in the number of patients on prednisone and csDMARDs during anti-TNF treatment. Conclusion: Remission with first-line anti-TNF treatment is an achievable goal in clinical practice, allowing a reduction in concomitant csDMARD and prednisone treatment