Immunoglobulin Gene Polymorphisms Are Susceptibility Factors in Clinical and Autoantibody Subgroups of the Idiopathic Inflammatory Myopathies

National Institute of Environmental Health Sciences, NIH, Bethesda, Maryland 20892, USA.
Arthritis & Rheumatology (Impact Factor: 7.76). 10/2008; 58(10):3239-46. DOI: 10.1002/art.23899
Source: PubMed


To investigate possible associations of GM and KM markers with adult and juvenile forms of the idiopathic inflammatory myopathies (IIMs) in Caucasian and African American patients.
We performed serologic analyses of polymorphic determinants associated with immunoglobulin gamma heavy chains (GM) and kappa light chains (KM) in large populations of Caucasian patients (n= 514 [297 adults and 217 children]) and African American patients (n=123 [73 adults and 50 children]) with IIM representing the major clinical and autoantibody groups.
For Caucasian patients with dermatomyositis (DM), the Gm 3 23 5,13 phenotype was a risk factor in both adults (odds ratio [OR] 2.2, corrected P [Pcorr]=0.020) and children (OR 2.2, Pcorr=0.0013). Of interest, the GM 13 allotype was a risk factor for juvenile DM in both Caucasian subjects (OR 3.9, Pcorr<0.0001) and African American subjects (OR 4.8, Pcorr=0.033). However, the Gm 1,3,17 5,13,21 phenotype was a risk factor for juvenile DM in Caucasian subjects but not African American subjects. Among the IIM autoantibody groups, Gm 3 23 5,13 was a risk factor in Caucasian adults with anti-Jo-1 autoantibodies (OR 3.4, Pcorr=0.0031), while the GM 3 allotype was protective in adults with anti-threonyl-transfer RNA synthetase or anti-U RNP autoantibodies (OR 0.1, Pcorr=0.047 and OR 0.2, Pcorr=0.034, respectively). In contrast, GM 6 was a risk factor in African American adults with anti-signal recognition particle autoantibodies (OR 7.5, Pcorr=0.041).
These data suggest that polymorphic alleles of GM and KM loci are differentially associated with IIM subgroups defined by age, ethnicity, clinical features, and autoantibody status, and expand the list of immune response genes that are possibly important in the pathogenesis of myositis.

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Available from: Lisa G. Rider Md, Aug 20, 2014
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    • "Immunoglobulin gene polymorphisms encoding constant regions of immunoglobulin gamma heavy (GM, 14q32.33) and kappa light (KM, 2p12) chains have been examined in a series of US Caucasian and African-American IIM cohorts [10,26,46]. A number of studies have examined individuals with allelic variants of specific GM/KM genes, in which raised titres of specific IgG antibody subclasses were present, against various antigenic epitopes of infectious disease agents or self-proteins [46]. "
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    ABSTRACT: This review summarizes the previous and current literature on the immunogenetics of idiopathic inflammatory myopathy (IIM) and updates the research progress that has been made over the past decade. A substantial part of the genetic risk for developing adult- and juvenile-onset IIM lies within the major histocompatibility complex (MHC), and a tight relationship exists between individual human leukocyte antigen alleles and specific serological subtypes, which in turn dictate clinical disease phenotypes. Multiple genetic regions outside of the MHC are increasingly being identified in conferring IIM disease susceptibility. We are still challenged with the task of studying a serologically and clinically heterogeneous disorder that is rarer by orders of magnitude than the likes of rheumatoid arthritis. An ongoing and internationally coordinated IIM genome-wide association study may provide further insights into IIM immunogenetics.
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