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  • Title: Galactose-deficient IgA1 in African Americans with IgA nephropathy: serum levels and heritability.
    Author: Hastings MC, Moldoveanu Z, Julian BA, Novak J, Sanders JT, McGlothan KR, Gharavi AG, Wyatt RJ.
    Journal: Clin J Am Soc Nephrol; 2010 Nov; 5(11):2069-74. PubMed ID: 20634323.
    Abstract:
    BACKGROUND AND OBJECTIVES: Serum levels of galactose-deficient IgA1 (Gd-IgA1) are elevated and heritable in Caucasian and Asian patients with IgA nephropathy (IgAN), but have not been characterized in African Americans (AA). Our objective was to determine whether serum Gd-IgA1 levels are increased in AA patients with IgAN and whether this is a heritable trait in this group. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: Blood and urine samples were obtained from 18 adult and 11 pediatric AA patients with biopsy-proven IgAN and from 34 of their first-degree relatives. Healthy controls included 150 Caucasian adults, 65 AA adults, 45 Caucasian children, and 49 AA children. Serum total IgA and Gd-IgA1 levels were measured in patients and controls. Significant differences between patient and control groups for serum total IgA, Gd-IgA1, and ratio of Gd-IgA1/total IgA were determined by the Mann-Whitney U test. Heritability was calculated using SOLAR. RESULTS: After stratifying by age, 7 of 11 pediatric and 9 of 18 adult AA patients with IgAN had serum Gd-IgA1 levels above the 95th percentile for age-appropriate AA controls. For first-degree relatives, the serum Gd-IgA1 level was >95th percentile for 1 of 8 when the patient's level was <95th percentile and 12 of 26 when the patient's level was >95th percentile (P = 0.116, Fisher exact test). Heritability was 0.74 (P = 0.007). CONCLUSIONS: Serum levels of Gd-IgA1 are often elevated in AA patients with IgAN and their first-degree relatives. Thus, aberrant IgA1 glycosylation is a heritable risk factor for IgAN in African Americans.
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