Lung fibrosis is uncommon in primary Sjögren's disease: A retrospective analysis of computed tomography features in 77 patients.

PURPOSE: The purpose of this study was to describe lung abnormalities observed on computed tomography (CT) in patients meeting the 2016 American College of Rheumatology/European League Against Rheumatism (EULAR) classification criteria for primary Sjögren's disease (pSD). MATERIALS AND METHODS: All patients with pSD seen between January 2009 and December 2020 in the day care centre of our National Reference Center for rare systemic autoimmune diseases, who had at least one chest CT examination available for review and for whom the cumulative EULAR Sjögren's Syndrome Disease Activity Index (cumESSDAI) could be calculated were retrospectively evaluated. CT examinations were reviewed, together with clinical symptoms and pulmonary functional results. RESULTS: Seventy-seven patients (73 women, four men) with a median age of 51 years at pSD diagnosis (age range: 17-79 years), a median follow-up time of 6 years and a median cumESSDAI of 7 were included. Sixty-six patients (86%) had anti-SSA antibodies. Thirty-three patients (33/77; 43%) had respiratory symptoms, without significant alteration in pulmonary function tests. Forty patients (40/77; 52%) had abnormal lung CT findings of whom almost half of them had no respiratory symptoms. Abnormalities on chest CT were more frequently observed in patients with anti-SSA positivity and a history of lymphoma. Air cysts (28/77; 36%) and mosaic perfusion (35/77; 35%) were the predominant abnormalities, whereas lung fibrosis was observed in five patients (5/77; 6%). CONCLUSION: More than half of patients with pSD have abnormal CT findings, mainly air cysts and mosaic perfusion, indicative of small airways disease, whereas lung fibrosis is rare, observed in less than 10% of such patients.

Autoantibodies versus Skin Fibrosis Extent in Systemic Sclerosis: A Case-Control Study of Inverted Phenotypes.

Objective: to describe the prevalences, characteristics, and survivals of patients with anti-topoisomerase 1 antibodies (ATA) and limited cutaneous systemic sclerosis (lSSc) and anti-centromere antibodies (ACA) and diffuse cutaneous systemic sclerosis (dSSc). Methods: patients with ATA lSSc or with ACA dSSc were included in a case-control retrospective study. Results: In our cohort of scleroderma, the prevalence of ACA dSSc and ATA lSSc was 1.1% (12/1040) and 8.9% (93/1040), respectively. ACA dSSc patients had less interstitial lung disease (ILD) (5 (41.7) vs. 74 (79.6); p < 0.01), more cardiac involvement, and more muscle involvement (3 (25) vs. 4 (4.3); p = 0.03 and 4 (33.3) vs. 4 (7.5); p = 0.02,) than ATA dSSc patients. ATA lSSc patients had a higher modified Rodnan skin score than ACA lSSc patients (4 [2−7.5] vs. 2 [0−5]; p < 0.01) and less cardiac or muscle involvement than ATA dSSc patients (6 (6.5) vs. 19 (20.4%); p < 0.01 and 15 (16.1) vs. 54 (58.1); p < 0.0001, respectively). The cumulative 5-year survival rate was 71% in ACA dSSc patients, 95% in ATA lSSc patients, 84% in ACA lSSc patients, and 66% in ATA dSSc patients (p < 0.0001). Conclusion: ATA lSSc and ACA dSSc have specific characteristics when compared to ATA dSSc or ACA lSSc. ATA lSSc patients have more ILD than ACA lSSc patients, and ATA dSSc patients have the worst prognosis. Overall, inverted phenotypes show the value of a patient assessment combining antibody and skin subset and should be considered as a separate group.

Serum neutralization of SARS-CoV-2 Omicron sublineages BA.1 and BA.2 in patients receiving monoclonal antibodies.

The severe acute respiratory syndrome coronavirus 2 Omicron BA.1 sublineage has been supplanted in many countries by the BA.2 sublineage. BA.2 differs from BA.1 by about 21 mutations in its spike. In this study, we first compared the sensitivity of BA.1 and BA.2 to neutralization by nine therapeutic monoclonal antibodies (mAbs). In contrast to BA.1, BA.2 was sensitive to cilgavimab, partly inhibited by imdevimab and resistant to adintrevimab and sotrovimab. We then analyzed sera from 29 immunocompromised individuals up to 1 month after administration of Ronapreve (casirivimab and imdevimab) and/or Evusheld (cilgavimab and tixagevimab) antibody cocktails. All treated individuals displayed elevated antibody levels in their sera, which efficiently neutralized the Delta variant. Sera from Ronapreve recipients did not neutralize BA.1 and weakly inhibited BA.2. Neutralization of BA.1 and BA.2 was detected in 19 and 29 out of 29 Evusheld recipients, respectively. As compared to the Delta variant, neutralizing titers were more markedly decreased against BA.1 (344-fold) than BA.2 (nine-fold). We further report four breakthrough Omicron infections among the 29 individuals, indicating that antibody treatment did not fully prevent infection. Collectively, BA.1 and BA.2 exhibit noticeable differences in their sensitivity to therapeutic mAbs. Anti-Omicron neutralizing activity of Ronapreve and, to a lesser extent, that of Evusheld is reduced in patients' sera.

Immunogenicity of BNT162b2 vaccine against the Alpha and Delta variants in immunocompromised patients with systemic inflammatory diseases.

OBJECTIVES: The emergence of strains of SARS-CoV-2 exhibiting increase viral fitness and immune escape potential, such as the Delta variant (B.1.617.2), raises concerns in immunocompromised patients. We aimed to evaluate seroconversion, cross-neutralisation and T-cell responses induced by BNT162b2 in immunocompromised patients with systemic inflammatory diseases. METHODS: Prospective monocentric study including patients with systemic inflammatory diseases and healthcare immunocompetent workers as controls. Primary endpoints were anti-spike antibodies levels and cross-neutralisation of Alpha and Delta variants after BNT162b2 vaccine. Secondary endpoints were T-cell responses, breakthrough infections and safety. RESULTS: Sixty-four cases and 21 controls not previously infected with SARS-CoV-2 were analysed. Kinetics of anti-spike IgG after BNT162b2 vaccine showed lower and delayed induction in cases, more pronounced with rituximab. Administration of two doses of BNT162b2 generated a neutralising response against Alpha and Delta in 100% of controls, while sera from only one of rituximab-treated patients neutralised Alpha (5%) and none Delta. Other therapeutic regimens induced a partial neutralising activity against Alpha, even lower against Delta. All controls and cases except those treated with methotrexate mounted a SARS-CoV-2 specific T-cell response. Methotrexate abrogated T-cell responses after one dose and dramatically impaired T-cell responses after two doses of BNT162b2. Third dose of vaccine improved immunogenicity in patients with low responses. CONCLUSION: Rituximab and methotrexate differentially impact the immunogenicity of BNT162b2, by impairing B-cell and T-cell responses, respectively. Delta fully escapes the humoral response of individuals treated with rituximab. These findings support efforts to improve BNT162b2 immunogenicity in immunocompromised individuals (ClinicalTrials.gov number, NCT04870411).