Mother–child blood group incompatibility and the risk of multiple sclerosis

Abstract

Sirs, Multiple sclerosis (MS) is an inflammatory disease of the central nervous system (CNS) characterized by myelin loss, varying degrees of axonal pathology and progressive neurological dysfunction [5]. Autoimmune mechanisms are thought to have major roles in the pathogenesis of MS [4], but the cause of the disease is not yet conclusively understood [5]. A maternal parent-of-origin effect in MS [3] has now been well demonstrated, but the biological basis of this remains unknown [7]. One possible explanation, however, is that during fetal and perinatal life, the immune system is developing and may be vulnerable to a variety of immunological triggers including mother–child blood group incompatibility. This could result in immune system dysfunction subsequently leading to autoimmune disease [1]. Consistent with this, type 1 diabetes, which is also a putative autoimmune disorder, has been shown to be associated with mother–child blood group incompatibility [1]. The population-based Canadian Collaborative Project on Genetic Susceptibility to Multiple Sclerosis (CCPGSMS) has been collecting perinatal data on MS index cases and spousal controls using telephone structured telephone interviews with appropriate consents [7]. Data specific for the question of mother–child blood group incompatibility were collected from mothers of index cases and controls. Data were analyzed by the Chi squared test and logistic regression. Information on blood group incompatibility (either ABO or Rhesus) as well as neonatal jaundice was available for 6,561 (4,948 female, 1,613 male) MS index cases and 2,472 (764 female, 1,708 male) spousal controls. There was no significant difference between mean ages of index cases and spousal controls. Two hundred and thirty (3.5%) of MS index cases had blood group incompatibility, not significantly different (p = 0.76) from controls (n = 90; 3.6%). The frequency of neonatal jaundice also did not differ significantly (p = 0.92) between cases (n = 956; 14.6%) and controls (n = 358; 14.5%). There is a preponderance of affected females in MS [6], and thus there is a corresponding over-representation of male spousal controls. If the trait of interest is sex-limited, then analysis by sex stratified cases and controls is important [8]. When comparing female cases and controls and male cases and controls separately, there were no significant differences (Table 1). Logistic regression confirmed this, showing an effect of female sex on the risk of MS (p \ 1 9 10) but no effect of neonatal jaundice (p = 0.67) or blood group incompatibility (p = 0.78). One potential route the maternal effect in MS could occur is via blood group incompatibility. The large MS index case sample size used in this study would, however, S. V. Ramagopalan D. A. Dyment S.-M. Orton G. C. Ebers Wellcome Trust Centre for Human Genetics, University of Oxford, Oxford, UK e-mail: sramagopalan@gmail.com