title: Maternal HLA class II compatibility in men with systemic lupus erythematosus.
abstract: OBJECTIVE
  Maternal-fetal cell transfer during pregnancy can lead to long-lasting microchimerism, which raises the question of whether microchimerism sometimes contributes to autoimmune disease later in life. In an experimental model, transfusion of parental lymphocytes homozygous for major histocompatibility complex alleles results in systemic lupus erythematosus (SLE). We identified male patients with SLE and healthy male subjects and their mothers in order to investigate the mother-son HLA relationship in SLE risk. Male subjects were selected in order to avoid confounding due to fetal microchimerism, which may occur in women.
  
  
  METHODS
  HLA genotyping for DRB1, DQA1, and DQB1 was conducted for sons and their mothers. Thirty men with SLE and their mothers were compared with 76 healthy men and their mothers.
  
  
  RESULTS
  Sons with SLE were HLA-identical with their mothers (bidirectionally compatible) for the basic HLA-DRB1 groups encoded by DRB1*01 through DRB1*14 more often than were healthy sons (odds ratio [OR] 5.0, P = 0.006). Each DRB1 group contains multiple allelic variants; male patients with SLE and their mothers often were identical for both DRB1 allelic variants (OR 3.2, P = 0.08). For DQA1 and DQB1, the ORs were 2.3 (P = 0.08) and 2.0 (P = 0.21), respectively. When analysis was limited to male subjects with SLE-associated HLA genes (encoding HLA-DR2 or HLA-DR3), the differences further increased for DRB1 basic groups (OR 7.2, P = 0.01), DRB1 alleles (OR 15.0, P = 0.018), DQA1 6.4 (P = 0.006), and DQB1 (OR 5.7, P = 0.027). No increase in (unidirectional) compatibility of the mother from the son's perspective was observed at any locus.
  
  
  CONCLUSIONS
  We observed increased bidirectional HLA class II compatibility of male SLE patients and their mothers compared with healthy men and their mothers. This observation implies that maternal microchimerism could sometimes be involved in SLE and therefore merits further investigation.
authors.affiliation: Fred Hutchinson Cancer Research Center and University of Washington, Seattle, USA. anne.stevens@seattlechildrens.org
authors.forename: Anne M
authors.initials: AM
authors.lastname: Stevens
authors.forename: Betty P
authors.initials: BP
authors.lastname: Tsao
authors.forename: Bevra H
authors.initials: BH
authors.lastname: Hahn
authors.forename: Katherine
authors.initials: K
authors.lastname: Guthrie
authors.forename: Nathalie C
authors.initials: NC
authors.lastname: Lambert
authors.forename: Allison J
authors.initials: AJ
authors.lastname: Porter
authors.forename: Tracy S
authors.initials: TS
authors.lastname: Tylee
authors.forename: J Lee
authors.initials: JL
authors.lastname: Nelson
mesh_terms: D000293:Adolescent; D000328:Adult; D002648:Child; D002675:Child, Preschool; D005192:Family Health; D005260:Female; D005787:Gene Frequency; D005802:Genes, MHC Class II / Q000235:genetics* / Q000276:immunology; D020022:Genetic Predisposition to Disease; D005838:Genotype; D006684:HLA-DR Antigens / Q000235:genetics* / Q000276:immunology; D059811:HLA-DRB1 Chains; D006648:Histocompatibility / Q000235:genetics* / Q000276:immunology; D006801:Humans; D008180:Lupus Erythematosus, Systemic / Q000235:genetics* / Q000276:immunology; D008297:Male; D008875:Middle Aged; D009035:Mothers
chemical_list: D006684:HLA-DR Antigens; D059811:HLA-DRB1 Chains