Early onset multisystem autoimmunity is commonly the defining feature of IPEX. Recurrent sinopulmonary infections and CVID-like phenotype were not previously recognized as a presentation in IPEX. Herein, we describe three extended family members with IPEX. In addition to autoimmunity, all three had a CVID-like presentation consisting of recurrent sinopulmonary infections, hypogammaglobulinemia and B-cell class switching defect. In vitro studies have shown that the B cell class switching defect is not B cell intrinsic. Additionally, a marked increase in circulating T follicular helper (cTFH) cells with high IFN-γ and IL-17 secretion on stimulation was noted in our patients. The dysregulated cTFH cells could contribute to a decreased B cell class switching. However, the exact mechanism of how expanded and dysregulated cTFH lead to B cell class switching defect and hypogammaglobulinemia in our patients is not clear. Our study could extend the clinical spectrum of IPEX to include a CVID-like presentation.

早期发作的多系统自身免疫通常是IPEX的定义特征。复发性肺肺感染和CVID样表型以前未被认为是IPEX的表现。在此，我们介绍了IPEX的三个大家庭成员。除自身免疫性外，所有三个患者均具有CVID样表现，包括复发性肺肺感染，低血球蛋白血症和B细胞类别转换缺陷。体外研究表明，B细胞类别转换缺陷不是B细胞固有的。此外，在我们的患者中发现在刺激时具有较高IFN-γ和IL-17分泌的循环T卵泡辅助细胞（cTFH）细胞明显增加。失调的cTFH细胞可能有助于减少B细胞类别的转换。然而，尚不清楚我们的患者中cTFH的扩展和失调如何导致B细胞类别转换缺陷和低球蛋白球蛋白血症的确切机制尚不清楚。我们的研究可以扩大IPEX的临床范围，使其包括类似CVID的表现。