Case#: 49-year-old woman

DiseaseAssertion: CTLA-4 deficiency-associated GLILD

FamilyInfo: Family history is negative for hereditary and immunological diseases

CasePresentingHPOs: HP:0031246, HP:0033709, HP:0002094

CaseHPOFreeText: Laboratory tests revealed decreased levels of serum globulin (IgG, IgA, and IgM) and pancytopenia. Serum soluble interleukin-2 receptor levels were elevated within the normal range for angiotensin-converting enzyme levels. Serum antibodies to human immunodeficiency virus (HIV) were within the normal CD4+ T-cell count limit at 1,079 /μL. A flow cytometric analysis demonstrated a decreased number of CD19+CD27+ memory B cells in the blood, with a selective decrease in IgG- and IgA-producing memory B cells. Chest radiography revealed bilateral infiltration of the lower lung fields while chest CT showed bilateral lower lobe reticular shadows as well as right middle lobe infiltrative and scattered nodular shadows in both the upper lobes. Bronchoalveolar lavage (BAL) showed increased cell counts (5.5×104/μL) and increased eosinophils, neutrophils, and lymphocytes in the cell fraction (eosinophils, 7%; neutrophils, 3%; lymphocytes, 25%; macrophages, 65%). The CD4/CD8 ratio in the lymphocytes was within the normal range (CD4/CD8 ratio: 1.06). A transbronchial lung biopsy revealed mild lymphocytic and eosinophilic infiltration of the cell septa. A pathological examination at low magnification revealed collapsed alveolar spaces with surrounding fibrotic changes, and at high magnification, thickened alveolar walls, nodule formation with lymphocyte and plasma cell infiltration, and lymphatic follicles were found. Polypoid plugs of loose organizing connective tissue (Masson bodies) within alveoli and small granulomas were also present. The infiltrated lymphocytes were CD3- or CD20-positive.

CaseNotHPOFreeText: Autoantibodies also tested negative. Bacterial and mycobacterial culture for chronic lower respiratory tract infections were negative. IgG4-positive cells were not detected. There was no neutrophil accumulation or presence of fungus, Gram-positive and/or Gram-negative bacteria, or acid-fast bacteria that would have suggested infection. No findings of vasculitis or malignant tumors were noted.

CasePreviousTesting: NR

GenotypingMethod: NR

PreviouslyPublished: NR

Variant: NM_005214.5:c.160G>A

ClinVar: 430905

CAID: CA350138187

gnomAD: NR

SupplementalData: Table, Fig 1a-c, Fig 2a-f