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HLA B*44

Neurology.2010 Aug 17;75(7):634-40.

HLA B*44: protective effects in MS susceptibility and MRIoutcome measures.Healy BC,Liguori M,Tran D,Chitnis T,Glanz B,Wolfish C,Gauthier S,Buckle G,Houtchens M,StazzoneL,Khoury S,Hartzmann R,Fernandez-Vina M,Hafler DA,Weiner HL,Guttmann CR,De Jager PL.

Source

Program in Translational NeuroPsychiatric Genomics, Department of Neurology, Brigham and Women's Hospital, 77

Avenue Louis Pasteur, NRB 168c, Boston, MA 02115, USA.

Abstract

OBJECTIVE:In addition to the main multiple sclerosis (MS) major histocompatibility complex (MHC) risk allele

(HLA DRB1*1501), investigations of the MHC have implicated several class I MHC loci

(HLA A, HLA B, and HLA C) as potential independent MS susceptibility loci. Here, we evaluate the

role of 3 putative protective alleles in MS: HLA A*02, HLA B*44, and HLA C*05.

METHODS:

Subjects include a clinic-based patient sample with a diagnosis of either MS or a clinically isolated

syndrome (n = 532), compared to subjects in a bone marrow donor registry (n = 776). All subjects

have 2-digit HLA data. Logistic regression was used to determine the independence of each allele's

effect. We used linear regression and an additive model to test for correlation between an allele and

MRI and clinical measures of disease course.

RESULTS:

After accounting for the effect of HLA DRB1*1501, both HLA A*02 and HLA B*44 are validated assusceptibility alleles (p(A*02) 0.00039 and p(B*44) 0.00092) and remain significantly associated with

MS susceptibility in the presence of the other allele. Although A*02 is not associated with MS

outcome measures, HLA B*44 demonstrates association with a better radiologic outcome both in

terms of brain parenchymal fraction and T2 hyperintense lesion volume (p = 0.03 for each outcome).

CONCLUSION:

The MHC class I alleles HLA A*02 and HLA B*44 independently reduce susceptibility to MS, but

only HLA B*44 appears to influence disease course, preserving brain volume and reducing the

burden of T2 hyperintense lesions in subjects with MS.

WhileHLA A*02 andHLA B*44 are clearly validated as protective haplotypes in this andother studies, we see evidence that only theHLA B*44 haplotype affects volumetric MRI

measures (BPF and T2 hyperintense lesion volume): on average, subjects with MS

withHLA B*44 alleles had a larger brain volume and a lower lesion burden than subjects

with MS who lacked this allele. Our secondary analysis of longitudinal data suggests that

these correlations may arise from a reduction in the rates of brain atrophy and T2 lesion

volume accumulation. Thus, the difference in brain volume at a subject's last MRI is less

likely to be due to differences in baseline brain volume. However, further work is needed

to confirm our observations relating these MS outcome measures andHLA B*44 as well

as an independent report of associations betweenHLA A*02 and measures of MS disease

course that we did not validate in our sample set

http://www.ncbi.nlm.nih.gov/pubmed/20713950http://www.ncbi.nlm.nih.gov/pubmed/20713950http://www.ncbi.nlm.nih.gov/pubmed?term=Healy%20BC%5BAuthor%5D&cauthor=true&cauthor_uid=20713950http://www.ncbi.nlm.nih.gov/pubmed?term=Healy%20BC%5BAuthor%5D&cauthor=true&cauthor_uid=20713950http://www.ncbi.nlm.nih.gov/pubmed?term=Liguori%20M%5BAuthor%5D&cauthor=true&cauthor_uid=20713950http://www.ncbi.nlm.nih.gov/pubmed?term=Liguori%20M%5BAuthor%5D&cauthor=true&cauthor_uid=20713950http://www.ncbi.nlm.nih.gov/pubmed?term=Liguori%20M%5BAuthor%5D&cauthor=true&cauthor_uid=20713950http://www.ncbi.nlm.nih.gov/pubmed?term=Tran%20D%5BAuthor%5D&cauthor=true&cauthor_uid=20713950http://www.ncbi.nlm.nih.gov/pubmed?term=Tran%20D%5BAuthor%5D&cauthor=true&cauthor_uid=20713950http://www.ncbi.nlm.nih.gov/pubmed?term=Tran%20D%5BAuthor%5D&cauthor=true&cauthor_uid=20713950http://www.ncbi.nlm.nih.gov/pubmed?term=Chitnis%20T%5BAuthor%5D&cauthor=true&cauthor_uid=20713950http://www.ncbi.nlm.nih.gov/pubmed?term=Chitnis%20T%5BAuthor%5D&cauthor=true&cauthor_uid=20713950http://www.ncbi.nlm.nih.gov/pubmed?term=Chitnis%20T%5BAuthor%5D&cauthor=true&cauthor_uid=20713950http://www.ncbi.nlm.nih.gov/pubmed?term=Glanz%20B%5BAuthor%5D&cauthor=true&cauthor_uid=20713950http://www.ncbi.nlm.nih.gov/pubmed?term=Glanz%20B%5BAuthor%5D&cauthor=true&cauthor_uid=20713950http://www.ncbi.nlm.nih.gov/pubmed?term=Glanz%20B%5BAuthor%5D&cauthor=true&cauthor_uid=20713950http://www.ncbi.nlm.nih.gov/pubmed?term=Wolfish%20C%5BAuthor%5D&cauthor=true&cauthor_uid=20713950http://www.ncbi.nlm.nih.gov/pubmed?term=Wolfish%20C%5BAuthor%5D&cauthor=true&cauthor_uid=20713950http://www.ncbi.nlm.nih.gov/pubmed?term=Wolfish%20C%5BAuthor%5D&cauthor=true&cauthor_uid=20713950http://www.ncbi.nlm.nih.gov/pubmed?term=Gauthier%20S%5BAuthor%5D&cauthor=true&cauthor_uid=20713950http://www.ncbi.nlm.nih.gov/pubmed?term=Gauthier%20S%5BAuthor%5D&cauthor=true&cauthor_uid=20713950http://www.ncbi.nlm.nih.gov/pubmed?term=Gauthier%20S%5BAuthor%5D&cauthor=true&cauthor_uid=20713950http://www.ncbi.nlm.nih.gov/pubmed?term=Buckle%20G%5BAuthor%5D&cauthor=true&cauthor_uid=20713950http://www.ncbi.nlm.nih.gov/pubmed?term=Buckle%20G%5BAuthor%5D&cauthor=true&cauthor_uid=20713950http://www.ncbi.nlm.nih.gov/pubmed?term=Buckle%20G%5BAuthor%5D&cauthor=true&cauthor_uid=20713950http://www.ncbi.nlm.nih.gov/pubmed?term=Houtchens%20M%5BAuthor%5D&cauthor=true&cauthor_uid=20713950http://www.ncbi.nlm.nih.gov/pubmed?term=Houtchens%20M%5BAuthor%5D&cauthor=true&cauthor_uid=20713950http://www.ncbi.nlm.nih.gov/pubmed?term=Houtchens%20M%5BAuthor%5D&cauthor=true&cauthor_uid=20713950http://www.ncbi.nlm.nih.gov/pubmed?term=Stazzone%20L%5BAuthor%5D&cauthor=true&cauthor_uid=20713950http://www.ncbi.nlm.nih.gov/pubmed?term=Stazzone%20L%5BAuthor%5D&cauthor=true&cauthor_uid=20713950http://www.ncbi.nlm.nih.gov/pubmed?term=Stazzone%20L%5BAuthor%5D&cauthor=true&cauthor_uid=20713950http://www.ncbi.nlm.nih.gov/pubmed?term=Stazzone%20L%5BAuthor%5D&cauthor=true&cauthor_uid=20713950http://www.ncbi.nlm.nih.gov/pubmed?term=Khoury%20S%5BAuthor%5D&cauthor=true&cauthor_uid=20713950http://www.ncbi.nlm.nih.gov/pubmed?term=Khoury%20S%5BAuthor%5D&cauthor=true&cauthor_uid=20713950http://www.ncbi.nlm.nih.gov/pubmed?term=Khoury%20S%5BAuthor%5D&cauthor=true&cauthor_uid=20713950http://www.ncbi.nlm.nih.gov/pubmed?term=Hartzmann%20R%5BAuthor%5D&cauthor=true&cauthor_uid=20713950http://www.ncbi.nlm.nih.gov/pubmed?term=Hartzmann%20R%5BAuthor%5D&cauthor=true&cauthor_uid=20713950http://www.ncbi.nlm.nih.gov/pubmed?term=Hartzmann%20R%5BAuthor%5D&cauthor=true&cauthor_uid=20713950http://www.ncbi.nlm.nih.gov/pubmed?term=Fernandez-Vina%20M%5BAuthor%5D&cauthor=true&cauthor_uid=20713950http://www.ncbi.nlm.nih.gov/pubmed?term=Fernandez-Vina%20M%5BAuthor%5D&cauthor=true&cauthor_uid=20713950http://www.ncbi.nlm.nih.gov/pubmed?term=Fernandez-Vina%20M%5BAuthor%5D&cauthor=true&cauthor_uid=20713950http://www.ncbi.nlm.nih.gov/pubmed?term=Hafler%20DA%5BAuthor%5D&cauthor=true&cauthor_uid=20713950http://www.ncbi.nlm.nih.gov/pubmed?term=Hafler%20DA%5BAuthor%5D&cauthor=true&cauthor_uid=20713950http://www.ncbi.nlm.nih.gov/pubmed?term=Hafler%20DA%5BAuthor%5D&cauthor=true&cauthor_uid=20713950http://www.ncbi.nlm.nih.gov/pubmed?term=Weiner%20HL%5BAuthor%5D&cauthor=true&cauthor_uid=20713950http://www.ncbi.nlm.nih.gov/pubmed?term=Weiner%20HL%5BAuthor%5D&cauthor=true&cauthor_uid=20713950http://www.ncbi.nlm.nih.gov/pubmed?term=Weiner%20HL%5BAuthor%5D&cauthor=true&cauthor_uid=20713950http://www.ncbi.nlm.nih.gov/pubmed?term=Guttmann%20CR%5BAuthor%5D&cauthor=true&cauthor_uid=20713950http://www.ncbi.nlm.nih.gov/pubmed?term=Guttmann%20CR%5BAuthor%5D&cauthor=true&cauthor_uid=20713950http://www.ncbi.nlm.nih.gov/pubmed?term=Guttmann%20CR%5BAuthor%5D&cauthor=true&cauthor_uid=20713950http://www.ncbi.nlm.nih.gov/pubmed?term=De%20Jager%20PL%5BAuthor%5D&cauthor=true&cauthor_uid=20713950http://www.ncbi.nlm.nih.gov/pubmed?term=De%20Jager%20PL%5BAuthor%5D&cauthor=true&cauthor_uid=20713950http://www.ncbi.nlm.nih.gov/pubmed?term=De%20Jager%20PL%5BAuthor%5D&cauthor=true&cauthor_uid=20713950http://www.ncbi.nlm.nih.gov/pubmed?term=De%20Jager%20PL%5BAuthor%5D&cauthor=true&cauthor_uid=20713950http://www.ncbi.nlm.nih.gov/pubmed?term=Guttmann%20CR%5BAuthor%5D&cauthor=true&cauthor_uid=20713950http://www.ncbi.nlm.nih.gov/pubmed?term=Weiner%20HL%5BAuthor%5D&cauthor=true&cauthor_uid=20713950http://www.ncbi.nlm.nih.gov/pubmed?term=Hafler%20DA%5BAuthor%5D&cauthor=true&cauthor_uid=20713950http://www.ncbi.nlm.nih.gov/pubmed?term=Fernandez-Vina%20M%5BAuthor%5D&cauthor=true&cauthor_uid=20713950http://www.ncbi.nlm.nih.gov/pubmed?term=Hartzmann%20R%5BAuthor%5D&cauthor=true&cauthor_uid=20713950http://www.ncbi.nlm.nih.gov/pubmed?term=Khoury%20S%5BAuthor%5D&cauthor=true&cauthor_uid=20713950http://www.ncbi.nlm.nih.gov/pubmed?term=Stazzone%20L%5BAuthor%5D&cauthor=true&cauthor_uid=20713950http://www.ncbi.nlm.nih.gov/pubmed?term=Stazzone%20L%5BAuthor%5D&cauthor=true&cauthor_uid=20713950http://www.ncbi.nlm.nih.gov/pubmed?term=Houtchens%20M%5BAuthor%5D&cauthor=true&cauthor_uid=20713950http://www.ncbi.nlm.nih.gov/pubmed?term=Buckle%20G%5BAuthor%5D&cauthor=true&cauthor_uid=20713950http://www.ncbi.nlm.nih.gov/pubmed?term=Gauthier%20S%5BAuthor%5D&cauthor=true&cauthor_uid=20713950http://www.ncbi.nlm.nih.gov/pubmed?term=Wolfish%20C%5BAuthor%5D&cauthor=true&cauthor_uid=20713950http://www.ncbi.nlm.nih.gov/pubmed?term=Glanz%20B%5BAuthor%5D&cauthor=true&cauthor_uid=20713950http://www.ncbi.nlm.nih.gov/pubmed?term=Chitnis%20T%5BAuthor%5D&cauthor=true&cauthor_uid=20713950http://www.ncbi.nlm.nih.gov/pubmed?term=Tran%20D%5BAuthor%5D&cauthor=true&cauthor_uid=20713950http://www.ncbi.nlm.nih.gov/pubmed?term=Liguori%20M%5BAuthor%5D&cauthor=true&cauthor_uid=20713950http://www.ncbi.nlm.nih.gov/pubmed?term=Healy%20BC%5BAuthor%5D&cauthor=true&cauthor_uid=20713950http://www.ncbi.nlm.nih.gov/pubmed/20713950

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Clin Immunol.2006 Jun;119(3):346-50. Epub 2006 Mar 20.

Increased frequency of HLA-B44 in recurrentsinopulmonary infections (RESPI).Johnston DT,Mehaffey G,Thomas J,Young KR Jr,Wiener H,Li J,Go RC,Schroeder HW Jr.

Source

University of Alabama at Birmingham, 1530 3rd Avenue South, Birmingham, AL 35294-3300, USA.

djohnston@peds.uab.edu

AbstractTo test whether MHC alleles associated with common variable immune deficiency (CVID) might also

be over-represented in patients with normal serum immunoglobulin levels who suffer with recurrent

sinopulmonary infections (RESPI), we identified 62 consecutive RESPI patients and compared

their HLA-B and HLA-DR antigen frequencies to those of 60 consecutive patients with CVID, 1627

Alabama Caucasian bone marrow donors, and 997,230 published US Caucasians. Either HLA-B44, -B8, -DR3(17), or -DR7 was present in 74% of the RESPI and 85% of the CVID patients. HLA-

B44 prevalence in particular proved identical between RESPI and CVID. When compared to US

Caucasians, the increased prevalence of the four HLAalleles proved significant at P < 0.0001, P