beta-Thalassemia trait association with autoimmune diseases: beta-globin locus proximity to the immunity genes or role of hemorphins?

Altinoz M. A., Gedikoglu G., DENİZ G.

IMMUNOPHARMACOLOGY AND IMMUNOTOXICOLOGY, vol.34, no.2, pp.181-190, 2012 (SCI-Expanded) identifier

  • Publication Type: Article / Review
  • Volume: 34 Issue: 2
  • Publication Date: 2012
  • Doi Number: 10.3109/08923973.2011.599391
  • Journal Indexes: Science Citation Index Expanded (SCI-EXPANDED), Scopus
  • Page Numbers: pp.181-190
  • Keywords: Thalassemia heterozygosity, autoimmunity, immunity genes at 11p15.5, inflammation, hemorphins, RENAL TUBULAR DYSFUNCTION, RHEUMATOID-ARTHRITIS, CELL-ACTIVATION, PROTEIN, MEMBER, STIM1, IDENTIFICATION, FIBROMYALGIA, DEFICIENCY, RESISTANCE
  • Istanbul University Affiliated: No


Thalassemia major continues to be a significant health problem for Mediterranean, Afro-Arabic countries, India and South Easth Asia. It was generally assumed that the beta-thalassemia heterozygotes do not bear significant medical risks except a mild microcytic anemia. Nonetheless, increasing number of reports associate beta-thalassemia trait with autoimmune conditions, nephritis, diabetes, arthritis, fibromyalgia and asthma. Available sparse data indicate reduced incidence of systemic lupus erythematosus (SLE) in beta-thalassemia heterozygotes; yet, if two conditions coexist, the SLE manifestations occur much severer. These associations make sense when considering that the hemoglobin beta-chain locus at 11p15.5 resides in close proximity to eight genes with profound roles in immune regulation: STIM1, CD151, TC21/RRAS2, SIGIRR/TOLL/IL1R8, pp52/LSP1 (lymphocyte specific protein), TRIM21, toll interacting protein (TOLLIP) and SLEN3. beta-Thalassemia trait accompaniment to autoimmune disease may be the result of haplotypal associations between the close proximity genes. An alternative explanation to thalassemia heterozygosity: autoimmune disease association may be the changed concentrations of hemorphins. Hemorphins are endogenous opioid peptides derived via proteolytical cleavage of hemoglobin. They are shown to bind diverse opioid receptors and act anti-inflammatory. Their reduced expression in thalassemia heterozygosity may explain a proinflammatory stage and autoimmunity vulnerability.