Pulmonary hypertension in a distinct IgG4-high phenotype of sarcoidosis: A case series

Sarcoidosis is a systemic disease of unknown etiology, characterized by granulomatous inflammation in various organs. Elevated serum Immunoglobulin G4 (IgG4) levels are typically associated with IgG4-related disease (IgG4-RD), characterized by plasma cell infiltration and fibrosis, but their role in sarcoidosis remains unclear. Given the fibro-inflammatory nature of both conditions, this study aimed to describe a cohort of sarcoidosis patients with elevated IgG4 levels and explore the potential clinical relevance of this finding. We retrospectively analyzed biopsy-confirmed sarcoidosis cases with measured serum IgG4 levels. Clinical data were gathered, including demographics, organ involvement, pulmonary function tests (PFTs), sarcoidosis-associated pulmonary hypertension (SAPH), and markers of autoimmunity. The study cohort included ten patients with a mean age of 50 ± 15 years, comprising six males and seven Black individuals. Two patients reported a family history of sarcoidosis; the mean body mass index (BMI) was 28.5 ± 5.7. Five patients were never smokers, and four were former smokers. Eight patients had lung involvement, two with advanced Scadding stage 4, four with airflow obstruction, and two with restriction physiology on PFT. Out of seven patients with echocardiography, five had SAPH. Other organ manifestation included ocular disease in three patients, joint involvement in two, liver disease in two, and heart disease in one. Autoimmune markers were present in five patients. These findings suggest a potential overlap between IgG4-RD and sarcoidosis. Further research is needed to clarify IgG4's role in sarcoidosis and whether elevated serum IgG4 identifies a subset of patients who may benefit from B-cell depletion therapies.