Immunology repertoire study of pulmonary sarcoidosis T cells in CD4+, CD8+ PBMC and tissue

Abstract

Sarcoidosis is a systemic granulomatous disorder highly related with immune response. The diversity and stability of the immune system could be measured by hypervariable complementarity-determining region 3 (CDR3) segments of the T cell receptor (TCR). Here we used a combination of multiplex PCR and next-generation sequencing to conduct a good quality analysis of the T-cell receptor BV complementarity-determining region 3 (TCR BV CDR3) gene in peripheral blood mononuclear cells (PBMCs) from 7 sarcoidosis patients and lung sarcoidosis tissue from 6 patients. The length distribution of CDR3 sequences identified a significant difference among CD4+, CD8+ and tissue samples. The analysis of Gini coefficient, Shannon entropy and HEC number showed that they all presents in sarcoidosis tissue group clones in a more skewed manner than that of in PMBCs groups. 2 nucleotide sequences and 2 amino acid sequences were shared by all samples. The comparison of TRBV, TRBJ usage and VJ combination frequency identified 2 TRBV genes, 2 TRBJ genes differentially expressed among different groups and different higher usage and lower usage of V-J combinations between each group.

Trained Innate Immunity Not Always Amicable

“…Sarcoidosis is a complex granulomatous disorder which is strongly related to immune response; however, its pathogenesis is still not completely understood. The immunological background of this disease involves the accumulation of activated macrophages and T-lymphocytes in affected organs, most commonly in the lung [101,102]. There is no information that epigenetic changes in monocytes could be associated with sarcoidosis, however both, occupational, environmental and infectious agents are involved in the development of this disorder [29].…”

The CSF in neurosarcoidosis contains consistent clonal expansion of CD8 T cells, but not CD4 T cells

“…Previous work suggested that CD4 T cells play a role in sarcoidosis (Drent et al, 2021). For example, lungs in sarcoidosis contain an expansion of T cell clones, consistent with an antigen-driven inflammatory response (Fu et al, 2017;Silver et al, 1996;Trentin et al, 1997). Furthermore, Lofgren's syndrome, a subtype of sarcoidosis characterized by fever, erythema nodosa, arthritis, and hilar lymphadenopathy, is genetically linked to the MHC class II allele HLA-DRB1*03:01 (Grunewald and Eklund, 2009) and is associated with shared T cell receptor (TCR) sequences in bronchoalveolar lavage fluids across individuals (Greaves et al, 2021;Grunewald et al, 1994;Mitchell et al, 2017), suggesting a shared pathogenic antigen that is recognized by CD4 T cells.…”

Identification and Validation of Hub Differential Genes in Pulmonary Sarcoidosis

“…Innovative experimental methods, such as microarrays utilizing extensive gene data, could offer fresh perspectives on possible pathogenic processes and related therapies for sarcoidosis [11,12]. Several sarcoidosis genomic studies have been carried out in various biosamples such as whole blood [13], peripheral blood mononuclear cells (PBMC) [12], bronchoalveolar lavage (BAL) cells [14], lung [15,16], and lymph nodes [17]. However, there are only a few studies investigating whether the gene expression of PBMC or whole blood, some of which is presumed to tra c to and from diseased tissues, was consistent with the tissue array results [18].…”