Haptoglobin Phenotypes in Systemic Sclerosis

Haptoglobin (Hp) is an acute phase protein, binding free hemoglobin and thus preventing catalysis of reactive oxygen species. The Hp encoding gene is polymorphic and three major subtypes, Hp1-1, Hp2-1 and Hp2-2 are the product of two genes HP1 and HP2. Hp2-2 phenotype is associated with increased prevalence of various systemic diseases, including autoimmune disorders. Moreover, Hp2-2 phenotype induces shift from Th1 to Th2 response and increases fibrotic processes. Systemic sclerosis (SSc) is a connective tissue disorder characterised by interstitial and perivascular fibrosis, due to different factors, including genetic, environmental, immunological and microchimeric factors. It has been reported that SSc is associated with Th2-type immune response and that Th1-type enhancement correlates with the improvement in SSc skin fibrosis.We examined 28 SSc outpatients (6 males, 22 females, mean age 51±6.3 years), diagnosed according to ARA criteria, and 27 control subjects (5 males, 23 females, mean age 49±7.1 years) to verify the Hp phenotype distribution. Our data support the hypothesis that SSc is a Th2-driven disorder and suggest that Hp 1-1 phenotype, less prevalent in patients respect to controls, is protective toward the disease. In fact, Hp 1-1 phenotype is biologically the most effective in suppressing immunomediated inflammatory responses associated with free hemoglobin.