case_images: PMC9831655_01
case_images: (A) Timeline of case 1. (B) Timeline of case 2. Steroids; AIHA, autoimmune hemolytic anemia; ITP, immune thrombocytopenic purpura; AI, autoimmune; HSCT, hematopoietic stem cell transplantation; CMV, cytomegalovirus; MC, myeloid chimerism; LC, lymphoid chimerism; CSA, cyclosporin; DLI, donor lymphocyte infusion; GLILD, granulomatous-lymphocytic interstitial lung disease; RTX, rituximab; IgRT, immunoglobulin replacement therapy; IBD, inflammatory bowel disease; GVHD, graft-versus-host disease.
case_images: fimmu-13-1070068-g001.jpg
case_images: PMC9831655_02_fimmu-13-1070068-g001.jpg
case_images: f1
case_images: We present a 21-year-old man with common variable immunodeficiency (CVID) and a phenotype of immune dysregulation similar to CTLA-4 haploinsufficiency characterized by autoimmune cytopenia, inflammatory bowel disease (IBD), lymphoproliferation (GLILD), autoimmune encephalitis, and humoral deficiency requiring multiple immunosuppressants ( Figure 1 ). However, CTLA-4 expression in FoxP3+ CD4+ T cells resembled that of CTLA-4-deficient patients, with a marked decrease in the CTLA-4hiFoxP3+CD4+ T cells ( Supplementary Figure S1 ). The timeline is depicted in  Figure 1 . Mixed chimerism persisted around 60%-70% in the lymphocytic lineage ( Figure 1 ).
case_images: Study of lung lesions of case 1. First image computed tomography (CT) scan showing multiple lung nodules. Second image wedge luyng biopsy demonstrated a non-necrotizing granulomatous inflammation concentrated bronchovasculocentrically and paraseptally [hematoxylin and eosin (H&E), 2x]. Third image fluorescencein-situ hybridization (FISH) using locus specific indentifier (LSI) SRY. In the lymphocytic infiltrates, up to 27% of the nuclei showed a green dot (CEP X) and a red dot (SRY), and 73% of the nuclei showed two green dots (CEP X), thus indicating that the majority of the lymphocytic infiltrate corresponded to the female donor.
case_images: fimmu-13-1070068-g002.jpg
case_images: PMC9831655_01_fimmu-13-1070068-g002.jpg
case_images: f2
case_images: After 5 days of fever and on antibiotics, computed tomography (CT) scan showed multiple lung nodules suggesting an infection or lymphoproliferative disorder ( Figure 2 ). T cells (female donor vs. male patient) were driving this inflammation, fluorescence in situ hybridization (FISH) X/Y was performed in the lung tissue to assess the chimerism in situ. The same pattern as in the blood ( Figure 2 ) was observed, ruling out enrichment of the patient's T cells in the granulomas.
case_images: PMC9831655_02
case_images: (A) Timeline of case 1. (B) Timeline of case 2. Steroids; AIHA, autoimmune hemolytic anemia; ITP, immune thrombocytopenic purpura; AI, autoimmune; HSCT, hematopoietic stem cell transplantation; CMV, cytomegalovirus; MC, myeloid chimerism; LC, lymphoid chimerism; CSA, cyclosporin; DLI, donor lymphocyte infusion; GLILD, granulomatous-lymphocytic interstitial lung disease; RTX, rituximab; IgRT, immunoglobulin replacement therapy; IBD, inflammatory bowel disease; GVHD, graft-versus-host disease.
case_images: fimmu-13-1070068-g001.jpg
case_images: PMC9831655_02_fimmu-13-1070068-g001.jpg
case_images: f1
case_images: We present a 21-year-old man with common variable immunodeficiency (CVID) and a phenotype of immune dysregulation similar to CTLA-4 haploinsufficiency characterized by autoimmune cytopenia, inflammatory bowel disease (IBD), lymphoproliferation (GLILD), autoimmune encephalitis, and humoral deficiency requiring multiple immunosuppressants ( Figure 1 ). However, CTLA-4 expression in FoxP3+ CD4+ T cells resembled that of CTLA-4-deficient patients, with a marked decrease in the CTLA-4hiFoxP3+CD4+ T cells ( Supplementary Figure S1 ). The timeline is depicted in  Figure 1 . Mixed chimerism persisted around 60%-70% in the lymphocytic lineage ( Figure 1 ).