PMID- 12850493
OWN - NLM
STAT- MEDLINE
DCOM- 20040430
LR  - 20191210
IS  - 1079-9796 (Print)
IS  - 1079-9796 (Linking)
VI  - 31
IP  - 1
DP  - 2003 Jul-Aug
TI  - Common variable immunodeficiency and IgG subclass deficiency in central Alabama 
      hemochromatosis probands homozygous for HFE C282Y.
PG  - 102-11
AB  - Eight hemochromatosis probands with HFE C282Y homozygosity had frequent, severe, 
      or unusual infections and common variable immunodeficiency (CVID) or 
      immunoglobulin (Ig) G subclass deficiency (IgGSD). Thus, we performed serum Ig 
      isotyping and other characterization of 43 additional unselected probands, 5 
      human leukocyte antigen (HLA)-identical siblings, and 240 consecutive CVID or 
      IgGSD index patients. C282Y allele frequencies were estimated in 58 CVID or IgGSD 
      index patients without hemochromatosis phenotypes and in 341 controls. HLA-A and 
      -B haplotypes and frequencies were determined in all 51 probands, 186 CVID or 
      IgGSD index patients without hemochromatosis phenotypes, and 751 controls. 
      Thirteen unselected probands (30%) had CVID or IgGSD. Among all 21 
      hemochromatosis probands with CVID (n = 4) or IgGSD (n = 17), Ig subclass 
      deficiency patterns were IgG(1) (n = 5), IgG(1) and IgG(3) (n = 6), IgG(3) (n = 
      9), and IgG(1), IgG(3), and IgG(4) (n = 1). IgG(2) or IgA deficiency was not 
      detected; one proband had IgM deficiency. Mean values of total IgG, IgG(1), and 
      IgG(3) were significantly lower in probands with CVID or IgGSD. Mean values of 
      age, transferrin saturation, and ferritin at diagnosis and phlebotomy units 
      required to induce iron depletion were similar in probands with or without CVID 
      or IgGSD; phlebotomy had no apparent effect on IgG levels. C282Y frequencies were 
      similar in CVID or IgGSD index cases without hemochromatosis phenotypes and in 
      controls. There was concordance of Ig and hemochromatosis phenotypes in probands 
      and respective HLA-identical siblings. Eight of 240 CVID or IgGSD index patients 
      had hemochromatosis phenotypes and C282Y homozygosity (3 vs 0.7% and 0.2% 
      controls; P < 0.0001, respectively). The frequency of A*03-B*07 was greater in 
      CVID and IgGSD index cases without hemochromatosis phenotypes than in controls 
      (0.0968 vs 0.0546, respectively; P = 0.0032). HLA-A*03-B*07 was the predominant 
      haplotype in probands grouped by presence or absence of CVID or IgGSD. Some 
      probands in each group were A*03-B*07 homozygotes; group A*03-B*07 frequencies 
      were similar. We conclude that serum IgG abnormalities characteristic of CVID or 
      IgGSD are common in hemochromatosis probands, and that the prevalence of 
      hemochromatosis is increased in CVID and IgGSD index cases. These observations 
      could be explained by the increased frequencies of HLA-A*03-B*07 in C282Y 
      homozygotes and in CVID and IgGSD, and by the common occurrence of putative CVID 
      or IgGSD allele(s) on haplotypes bearing C282Y.
FAU - Barton, James C
AU  - Barton JC
AD  - Southern Iron Disorders Center, Birmingham, AL, USA. ironmd@dnamail.com
FAU - Bertoli, Luigi F
AU  - Bertoli LF
FAU - Acton, Ronald T
AU  - Acton RT
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - United States
TA  - Blood Cells Mol Dis
JT  - Blood cells, molecules & diseases
JID - 9509932
RN  - 0 (HFE protein, human)
RN  - 0 (HLA Antigens)
RN  - 0 (Hemochromatosis Protein)
RN  - 0 (Histocompatibility Antigens Class I)
RN  - 0 (Membrane Proteins)
SB  - IM
MH  - Adult
MH  - Alabama
MH  - Common Variable Immunodeficiency/complications/epidemiology/*genetics
MH  - Family Health
MH  - Female
MH  - Gene Frequency
MH  - HLA Antigens/analysis/genetics
MH  - Hemochromatosis/complications/epidemiology/*genetics
MH  - Hemochromatosis Protein
MH  - Histocompatibility Antigens Class I/*genetics
MH  - Homozygote
MH  - Humans
MH  - IgG Deficiency/complications/epidemiology/*genetics
MH  - Incidence
MH  - Infections
MH  - Male
MH  - Membrane Proteins/*genetics
MH  - Middle Aged
MH  - *Mutation, Missense
EDAT- 2003/07/10 05:00
MHDA- 2004/05/01 05:00
CRDT- 2003/07/10 05:00
PHST- 2003/07/10 05:00 [pubmed]
PHST- 2004/05/01 05:00 [medline]
PHST- 2003/07/10 05:00 [entrez]
AID - S1079979603001165 [pii]
AID - 10.1016/s1079-9796(03)00116-5 [doi]
PST - ppublish
SO  - Blood Cells Mol Dis. 2003 Jul-Aug;31(1):102-11. doi: 
      10.1016/s1079-9796(03)00116-5.