Genetic and immunologic analysis of a family containing five patients with common-variable immune deficiency or selective IgA deficiency

Journal Article · Sun Nov 01 04:00:00 EST 1992 · Journal of Clinical Immunology; (United States)

DOI:https://doi.org/10.1007/BF00918852· OSTI ID:6441090

Ashman, R F; Kemp, J D; Yokoyama, W M ^[1]; Zhu, Z B; Cooper, M D; Volanakis, J E ^[2]

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1. Univ. of Iowa College of Medicine, Iowa City (United States)
2. Univ. of Alabama, Birmingham (United States)

A family with 13 members included 2 subjects with selective IgA deficiency (IgA-D) and 3 subjects with common-variable immune deficiency (CVID), diseases which usually occur sporadically. Reciprocal combinations of B and T cells in vitro between one normal and two immune-deficient family members and normal subjects revealed that defective Ig synthesis was determined by the B cells, while the patient T cells functioned normally. Normal T helper and suppressor function was demonstrated even in one patient with CVID who developed a T-cell lymphoproliferative disorder associated with elevated IgM; this patient's B cells made only IgM in vitro. Immune deficiencies were inherited in this family in a pattern consistent with an autosomal dominant trait with incomplete penetrance. All the immune-deficient patients in this family possessed at least one copy of an MHC haplotype previously shown to be abnormally frequent in IgA-D and CVID: HLA-DQB1*0201, HLA-DR3, C4B-Sf, C4A-deleted, G11-15, Bf-0.4, C2-a, HSP70-7.5, TNF[alpha]-5, HLA-B8, and HLA-A1. The patient who developed the lymphoproliferative disorder was homozygous for this haplotype. Four immunologically normal members, one of whom was 80 years old, also possessed this MHC haplotype, indicating that its presence is not sufficient for disease expression. A small segment of another MHC haplotype associated with Ig deficiency in the population also occurred in this family, but it was not associated with immune deficiency. The presence of neutral amino acids at position 57 of DQ[beta], previously correlated with IgA-D, was associated with disease in this family approximately to the same degree reported previously in unrelated patients. Thus the expression of immunodeficiency in individuals bearing a disease-associated MHC haplotype appears to require either additional genes or an environmental trigger.

• OSTI ID: 6441090
• Journal Information: Journal of Clinical Immunology; (United States), Journal Name: Journal of Clinical Immunology; (United States) Vol. 12:6; ISSN JCIMDO; ISSN 0271-9142
• Country of Publication: United States
• Language: English

Related Subjects

550400* -- Genetics
551000 -- Physiological Systems
59 BASIC BIOLOGICAL SCIENCES
ANIMAL CELLS
ANTIGENS
BIOLOGICAL MATERIALS
BIOLOGY
BIOSYNTHESIS
BLOOD
BLOOD CELLS
BODY FLUIDS
CONNECTIVE TISSUE CELLS
DISEASES
GENE MUTATIONS
GENETICS
GLOBULINS
HISTOCOMPATIBILITY COMPLEX
IMMUNE SYSTEM DISEASES
IMMUNOGLOBULINS
LEUKOCYTES
LYMPHOCYTES
MATERIALS
MUTATIONS
ORGANIC COMPOUNDS
PROTEINS
SOMATIC CELLS
SYNTHESIS