Differences between CVID Granulomatosis and Sarcoidosis: Clinical, Immunological and Histopathological Comparison

Abstract Common variable immunodeficiency granulomatous disease (CVID-GD) is a serious complication that occurs in 8–22% of CVID patients and can mimic sarcoidosis with which it shares certain clinical, biological and radiological features. However, no study to date has compared the two pathologies immunologically and histologically. Then, we analyzed the blood cell immunohistochemical-labeling profiles and the immunological-histological features of different biopsy samples from 10 patients with CVID-GD and compared them to those of with biopsy-proven sarcoidosis. Specifically, we wanted to know whether or not the signaling abnormalities observed in sarcoidosis granulomas are also present in CVID. The CVID-GD immunological profile differs markedly from that of sarcoidosis, with a profound memory-cell deficit, strong CD8 + T-cell activation and altered balance in follicular helper-T cells (TFH) subsets in the blood. Morphological differences were found between CVID-GD histology and classical sarcoidosis, mainly the former’s notable/extensive lymphoid hyperplasia associated with granulomas not observed in the latter. All organs involved with CVID-GD contained several TFH1 cells the granulomatosis, while TFH lymphocytes were inconstantly and more weakly expressed in sarcoidosis. Moreover, CVID and sarcoidosis granulomas expressed the signal transducer and activator of transcription (STAT)1 and STAT3 factors, regardless of the organ studied and without any significant difference between them. Our results suggest that the macrophage-activation mechanism in CVID resembles that of sarcoidosis, thereby suggesting that JAK-STAT-pathway blockade might be useful in currently difficult-to-treat CVID-GD.