PMC9352891_01
Laboratory trend in patient 1. 6MP, 6-mercaptopurine; ADA, adalimumab; GFD, gluten-free diet; IVIg, intravenous immunoglobulin; MTX, methotrexate.
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Over the subsequent decade, her TTG IgA slowly trended downward but remained positive (  Figure 1  ), and she continued to have diarrhea and secondary hypokalemia, iron deficiency anemia, and poor growth, intermittently requiring hospitalization for dehydration and electrolyte derangements in the setting of diarrheal output sometimes exceeding 6 L per day. IgG (nadir 342 mg/dl, normal range 639-1,344 mg/dl), low IgA ( Figure 1 ), and negative titers to varicella-zoster virus and mumps despite complete vaccination. Immunologic evaluation was also notable for low switched memory B cells (CD19+CD27+IgD- 1.40%, normal range 8.3%-27.8%) and low unswitched memory B cells (CD19+CD27+IgD+ 4.90%, normal range 7.0%-23.8%).
Histopathology findings in patient 1. (A) Duodenal mucosa with total villous atrophy, crypt hyperplasia, and patchy intraepithelial lymphocytosis, suggestive of celiac disease. (B) Normal duodenal mucosa, two years into treatment with abatacept.
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Histopathology continued to show changes consistent with celiac disease (  Figure 2A  ). She has had one follow-up EGD and ileocolonoscopy, which were grossly and histologically normal ( Figure 2B ).
Reduced CTLA4 expression in unstimulated memory regulatory T cells (Tregs) in patients 1 and 2 compared to healthy controls. Flow cytometry data gated on live/CD4+/Foxp3+. Representative expression of total CTLA4 in Tregs in patient 1 compared to healthy control (A) and patient 2 compared to healthy control (B). Percentages shown in quadrants, with percentage CD45RA- (memory) Tregs expressing CTLA4 highlighted in red.
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Immunophenotyping by flow cytometry confirmed absent expression of CTLA4 on memory Tregs ( Figure 3B ).
PMC9352891_02
Reduced CTLA4 expression in unstimulated memory regulatory T cells (Tregs) in patients 1 and 2 compared to healthy controls. Flow cytometry data gated on live/CD4+/Foxp3+. Representative expression of total CTLA4 in Tregs in patient 1 compared to healthy control (A) and patient 2 compared to healthy control (B). Percentages shown in quadrants, with percentage CD45RA- (memory) Tregs expressing CTLA4 highlighted in red.
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Immunophenotyping by flow cytometry confirmed absent expression of CTLA4 on memory Tregs ( Figure 3B ).