PMC8847221_01
(A) Family pedigree of the patient. (B) Electrophoretogram of the detected novel pathogenic variant in comparison with the wild-type FOXP3 sequence. (C) A schematic diagram of the disease course. UPC, urine protein-creatinine. (D) FOXP3 mutation analysis.
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F1
He had a remarkable past medical history (Figure 1C): he was diagnosed with autoimmune hemolysis 10 years ago, chronic otitis media and bronchiectasis 3 years ago, and repeated diarrhea and alternative constipation with hair loss in recent years (Figure 2A). 2 weeks ago, his diarrhea aggravated to 5-6 times per day, with medium volume of dilute watery stools, with no blood and stench. The pedigree is shown in Figure 1A. Compared with the reference sequence (hg19), a missense variant, located in chr X:4 9 11 1 9 36, was detected in exon 8 of FOXP3 (c.770A > C (p.Gln257Pro); N M _0 1 4 0 09) (Figures 1B,D) in both the boy and his mother.
Manifestations caused by autoimmune disorders in different organ systems. (A) The patient presented with alopecia areata. Chest CT showed signs of bronchiectasis, and abdominal CT showed swollen and thickened ileocecal and colon walls and enlarged lymph nodes. (B,C) Colonoscopic findings and pathological changes in different parts of the intestine (ileocecal junction, ascending colon, descending colon, sigmoid colon, rectum). Magnification: (B,C) x200-400.
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F2
He had a remarkable past medical history (Figure 1C): he was diagnosed with autoimmune hemolysis 10 years ago, chronic otitis media and bronchiectasis 3 years ago, and repeated diarrhea and alternative constipation with hair loss in recent years (Figure 2A). 2 weeks ago, his diarrhea aggravated to 5-6 times per day, with medium volume of dilute watery stools, with no blood and stench. Abdominal ultrasound and CT showed swollen and thickened ileocecal and colon walls and enlarged lymph nodes (Figure 2A). Thoracic high-resolution CT (HRCT) reported bronchiectasis and pneumonia mainly in the lingual lobe of the left lung and the middle lobe of the right lung (Figure 2A). Colonoscopy revealed particulate hyperplasia and submucosal hemorrhage in the terminal ileum, longitudinal ulcer in the sigmoid colon and descending colon, and erosive mucosa in the rectum (Figures 2B,C).
Light and electron microscopy findings and results of immunohistochemistry studies. (A) HE staining did not detect any crescent, PASM staining revealed spike-like structures deposited in the basement membrane, and Masson staining reported eosinophilic deposition in the basement. (B) Immunoglobulin (Ig) G, Ig A, C3, and albumin deposits identified at the glomerular capillary wall by immunohistochemical staining. (C) Electron microscopy confirms the diagnosis of MN. Magnification: (A,B) x200-400, (C) x2,500.
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F3
Pathologic examinations including immunofluorescence (IF), electron microscope, and histological examinations were conducted, in which IF revealed IgG (+++), IgA (+-), IgM (+), C3 (++), C1q (+), Fib (-), ALB (+), IgG1 (+++), IgG2 (+-), IgG3 (+-), IgG4 (++), PLA2R (+-), and THSD7A (-) granule deposition (Figure 3B). Electron microscopy showed that the basement membrane of glomerular capillary loop was irregularly thickened, about 240-1,100 nm (Figure 3C); segmental proliferation of mesangial cells and stroma in the glomerular mesangial area; and podocyte foot process diffuse fusion (>80%). Under a light microscope, the appearance of capillary loop was rigid, the segmental mesangial area was slightly widened, and there was no obvious mesangial cell proliferation; PASM staining revealed spike-like structure on the epithelial side of basement membrane of glomerular capillary loop; Masson staining reported eosinophilic deposition of subcutaneous eosinophils on the basement membrane of glomerular capillary loop (Figure 3A).