Morphological and molecular comparison of HIV-associated and sporadic inclusion body myositis

Abstract

Objective The molecular characteristics of sporadic inclusion body myositis (sIBM) have been intensively studied, and specific patterns on the cellular, protein and RNA level have emerged. However, these characteristics have not been studied in the context of HIV-associated IBM (HIV-IBM). In this study, we compared clinical, histopathological, and transcriptomic patterns of sIBM and HIV-IBM. Methods In this cross-sectional study, we compared patients with HIV-IBM and sIBM based on clinical and morphological features as well as gene expression levels of specific T-cell markers in skeletal muscle biopsy samples. Non-disease individuals served as controls (NDC). Cell counts for immunohistochemistry and gene expression profiles for quantitative PCR were used as primary outcomes. Results 14 muscle biopsy samples (7 HIV-IBM, 7 sIBM) of patients and 6 biopsy samples from NDC were included. Clinically, HIV-IBM patients showed a significantly lower age of onset and a shorter period between symptom onset and muscle biopsy. Histomorphologically, HIV-IBM patients showed no KLRG1+ or CD57+ cells, while the number of PD1+ cells did not differ significantly between the two groups. All markers were shown to be significantly upregulated at gene expression level with no significant difference between the IBM subgroups. Conclusion Despite HIV-IBM and sIBM sharing important clinical, histopathological, and transcriptomic signatures, the presence of KLRG1+ cells discriminated sIBM from HIV-IBM. This may be explained by longer disease duration and subsequent T-cell stimulation in sIBM. Thus, the presence of TEMRA cells is characteristic for sIBM, but not a prerequisite for the development of IBM in HIV+ patients.

The role of KLRG1: a novel biomarker and new therapeutic target

“…Since KLRG1 inhibits mTOR signaling through the PI3K/AKT pathway, the lack of KLRG1 expression on TCRαβ + CD4 − CD8 − double-negative T-cells in ALPS patients leads to overactivity of the mTOR pathway, resulting in abnormal lymphocyte proliferation [ 56 ]. In conclusion, these studies suggest that KLRG1 is mostly positively correlated with disease severity in autoimmune diseases [ 18 , 81 ], can serve as a marker of disease progression in patients with IBM [ 27 , 85 ] and SLE [ 80 ], and has potential as a therapeutic target in patients with IBM [ 79 ]. Targeting KLRG1 + lymphocytes may be a promising strategy for developing therapeutic agents for treating autoimmune diseases [ 18 , 79 ].…”