STAT expression and TFH1 cells in CVID granulomatosis and sarcoidosis: immunological and histopathological comparisons

Abstract

Granulomatous disease is a serious complication of common variable immunodeficiency (CVID-GD) that occurs in 8-22% of these patients and can mimic sarcoidosis, with which it shares certain clinical, biological, and radiological features. However, few studies to date have compared the two pathologies immunologically and histologically. Therefore, we analyzed the immunological-histological findings for different tissue samples from ten patients with CVID-GD and compared them to those of biopsy-proven sarcoidosis. Specifically, we wanted to know whether or not the signaling abnormalities observed in sarcoidosis granulomas are also present in CVID-GD. Morphological differences were found between CVID-GD histology and classical sarcoidosis: mainly, the former's notable lymphoid hyperplasia associated with granulomas not observed in the latter. All CVID-GD involved organs contained several follicular helper-T (TFH) cells within the granulomatosis, while those cells were inconstantly and more weakly expressed in sarcoidosis. Moreover, CVID and sarcoidosis granulomas expressed the phosphorylated-signal transducer and activator of transcription (pSTAT)1 and pSTAT3 factors, regardless of the organ studied and without any significant difference between entities. Our results suggest that the macrophage-activation mechanism in CVID resembles that of sarcoidosis, thereby suggesting that Janus kinase (JAK)-STAT-pathway blockade might be useful in currently difficult-to-treat CVID-GD.

Keywords: Common variable immunodeficiency; Granulomatosis; Hypogammaglobulinemia; STAT1; STAT3.