title: Frequency of concurrent autoimmune disorders in patients with autoimmune hepatitis: effect of age, gender, and genetic background.
abstract: BACKGROUND
  Concurrent autoimmune disorders (CAIDs) have been shown to occur in 22% to 34% of the patients with autoimmune hepatitis (AIH). Their presence has been linked to female gender, older age, and to certain HLA antigens, namely HLA-A11, DRB1*04, and DRB4*01.
  
  
  OBJECTIVE
  To assess the frequency and nature of CAID in Brazilian patients with AIH types 1 (AIH-1) and 2 (AIH-2) and to investigate the influence of age, gender, and genetic background in their occurrence.
  
  
  METHODS
  The presence and nature of CAID was studied in 143 patients [117 females, median age 11 (1.3 to 69)] with AIH-1 (n=125) and AIH-2 (n=28). HLA typing and tumor necrosis factor alpha gene promoter and exon 1 cytotoxic T lymphocyte associated antigen 4 (CTLA-4) gene polymorphisms were determined by polymerase chain reaction-based techniques.
  
  
  RESULTS
  The frequency of CAID was similar in patients with AIH-1 (14%) and AIH-2 (18%), but their nature was shown to vary. Arthritis was seen in half of the patients (n=8) with CAID and AIH-1 and in none of those with AIH-2. Subjects with AIH-1 and CAID were shown to be older [24 (1.3 to 61) vs. 11 (1.3 to 69) y, P=0.02] and to have more often circulating antinuclear antibody (76% vs. 40%, P=0.008) and less frequently antiactin antibodies (33% vs. 75%, P=0.008) when compared with their counterparts without CAID. No particular HLA-DR and DQ alleles, as well as tumor necrosis factor alpha and CTLA-4 genotypes, were associated with CAID.
  
  
  CONCLUSIONS
  The nature, but not the frequency, of CAID was shown to vary in AIH-1 and AIH-2. In subjects with AIH-1, CAID was linked to older subjects and to the presence of antinuclear antibody. No predisposition to CAID was associated to HLA-DRB1*04 or DDB4*01 alleles. The observed lower frequency of CAID could be attributed to the lower age of disease onset in Brazilians and to differences in HLA-encoded susceptibility to AIH-1 observed in South America.
authors.affiliation: Portuguese Hospital of Salvador, Bahia, Brazil. plbbr@uol.com.br
authors.forename: Paulo Lisboa
authors.initials: PL
authors.lastname: Bittencourt
authors.forename: Alberto Queiroz
authors.initials: AQ
authors.lastname: Farias
authors.forename: Gilda
authors.initials: G
authors.lastname: Porta
authors.forename: Eduardo L R
authors.initials: EL
authors.lastname: Cançado
authors.forename: Irene
authors.initials: I
authors.lastname: Miura
authors.forename: Renata
authors.initials: R
authors.lastname: Pugliese
authors.forename: Jorge
authors.initials: J
authors.lastname: Kalil
authors.forename: Anna C
authors.initials: AC
authors.lastname: Goldberg
authors.forename: Flair J
authors.initials: FJ
authors.lastname: Carrilho
mesh_terms: D000293:Adolescent; D000328:Adult; D000367:Age Factors; D000368:Aged; D000483:Alleles; D015703:Antigens, CD / Q000235:genetics* / Q000276:immunology; D000943:Antigens, Differentiation / Q000235:genetics* / Q000276:immunology; D001323:Autoantibodies / Q000276:immunology; D001938:Brazil / Q000453:epidemiology; D060908:CTLA-4 Antigen; D002648:Child; D002675:Child, Preschool; D003093:Colitis, Ulcerative / Q000150:complications / Q000453:epidemiology* / Q000235:genetics; D004247:DNA / Q000235:genetics*; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D005500:Follow-Up Studies; D020022:Genetic Predisposition to Disease / Q000235:genetics*; D005838:Genotype; D006684:HLA-DR Antigens / Q000235:genetics; D059811:HLA-DRB1 Chains; D059826:HLA-DRB3 Chains; D059845:HLA-DRB4 Chains; D019693:Hepatitis, Autoimmune / Q000150:complications* / Q000235:genetics / Q000276:immunology; D006650:Histocompatibility Testing; D006801:Humans; D007141:Immunoglobulin Fc Fragments; D015994:Incidence; D007223:Infant; D008297:Male; D008875:Middle Aged; D011110:Polymorphism, Genetic; D020133:Reverse Transcriptase Polymerase Chain Reaction; D012307:Risk Factors; D013967:Thyroiditis, Autoimmune / Q000150:complications / Q000453:epidemiology* / Q000235:genetics; D014409:Tumor Necrosis Factor-alpha / Q000235:genetics
chemical_list: D015703:Antigens, CD; D000943:Antigens, Differentiation; D001323:Autoantibodies; D060908:CTLA-4 Antigen; C556706:CTLA4 protein, human; D006684:HLA-DR Antigens; D059811:HLA-DRB1 Chains; D059826:HLA-DRB3 Chains; D059845:HLA-DRB4 Chains; D007141:Immunoglobulin Fc Fragments; D014409:Tumor Necrosis Factor-alpha; D004247:DNA