title: The clinical characterisation of systemic lupus erythematosus in a Far North Queensland Indigenous kindred.
abstract: The aetiology of systemic lupus erythematosus (SLE) is thought to involve both genetic and environmental factors. In other complex diseases, analysis of large multi-case families has resulted in insights into biological mechanisms. We have sought to characterise the members of an extended Indigenous family, five of whom have been diagnosed with SLE. Pedigree members were evaluated using the Lupus Screening Questionnaire, clinical interviews and medical records. Participants contributed blood and urine samples for laboratory analysis. A Mendelian pattern of inheritance was not observed. The five affected members (all female) shared two American College of Rheumatology criteria (positive ANA and arthritis) but showed a wide variety of other SLE manifestations. Disease onset, severity and progression were discordant. Including the five individuals with SLE, 15 blood relatives and two non-consanguineous spouses had autoimmune manifestations. Autoimmune haemolytic anaemia (one case), idiopathic thrombocytopenic purpura (ITP) (one case) and hypothyroidism (two cases) were observed in non-SLE affected individuals. Anti-nuclear antibodies were present in 12 blood relatives and one non-consanguineous spouse. Infections (especially of the skin) were observed to be common in the kindred. The lack of clear Mendelian inheritance or phenotypic concordance makes a rare monogenic explanation for SLE unlikely in this family. The finding of familial autoimmunity associated with SLE further supports the hypothesis that a common genetic pathway can precipitate autoimmunity, with further genes and possible environmental factors interacting to produce the eventual phenotype. Future genetic linkage studies may reveal a rare 'autoimmune gene' variant in this kindred.
authors.affiliation: Prince of Wales Hospital, Randwick, New South Wales, Australia.
authors.forename: J A
authors.initials: JA
authors.lastname: Mason
authors.forename: D
authors.initials: D
authors.lastname: Bossingham
mesh_terms: D000293:Adolescent; D000328:Adult; D005260:Female; D020022:Genetic Predisposition to Disease; D006801:Humans; D008180:Lupus Erythematosus, Systemic / Q000453:epidemiology / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D010375:Pedigree; D011793:Queensland; D012720:Severity of Illness Index; D055815:Young Adult