Association Between IgA Immunoglobulin Level and Response to Treatment for Immune Thrombocytopenia (ITP).

ITP is a disorder of antibody mediated destruction and inhibition of production of platelets. ITP is idiopathic as it is unclear what immune factors relate to disease severity and response to treatment. We hypothesize that immune dysregulation represented by abnormal immunoglobulins especially elevated IgA may increase the risk of disease or failure to respond to treatment.

We performed a retrospective analysis of the Platelet Disorder Center master list, encompassing all of the patients with ITP seen at the Platelet Disorder Center in the past 10 years. The data includes demographics, use of and response to treatments, and certain selected laboratory values including levels of gamma globulins. The subject's serum IgA levels were observed for differences in response to treatment; IgG was not evaluated because of the use of IVIG. The analysis was performed using STATA statistical software and the Chi squared test.

In total, data was available for 946 subjects with ITP of which 778 had baseline immunoglobulin data. The population was predominantly female (62%) and young with a mean age of 33.4 (SD 23.1) and ranged from less than 1 year old to 94 years of age. IgA mean was 188mg/dl (SD 136). 109 subjects (14%) had an elevated IgA (normal range 70-312). Subjects with an IgA greater than 312 were older than the general population with a mean age 48 (SD 19.4). Subjects with an IgA level greater than mean had a significantly increased chance of failing to respond to standard treatment (steroids, Win-Rho or IVIG) than patients with an IgA level lower than mean (13% vs. 8% p=0.05) and a trend towards failure to respond to individual treatments (rituxan 46% vs. 38% p =0.193, Win-Rho 27% vs. 21% p =0.25, IVIG 24% vs. 16% p= 0.07). In contrast patients with an IgA greater than mean were more likely to respond to splenectomy than patients with IgA less than mean (32.1% vs. 18.1% p=0.045). Subjects with an IgA greater than mean also had an increased risk of having a major bleed (9% vs. 6% p = 0.037). There was no difference in response to standard treatment in subjects with IgA below the lower limit of normal (70mg/dl) relative to subjects with a normal or elevated IgA (8% vs. 11% p= 0.69). Subjects with an IgA above the upper limit of normal (312mg/dl) did not have a significant increase in their chance to fail standard treatment relative to the rest of the study population (9% vs. 11% p =0.12). Subjects older than 65 were more likely to fail to respond to standard treatment than patients under 65 (20% vs. 8% p =0.01) and have an elevated IgA (20% vs. 13% p =0.034). Subjects older than 65 had a non-significant increase in risk of failure to respond to treatment if IgA was greater than mean (26% vs. 14% p= 0.16). This trend was less pronounced in subjects under 65 (10% vs. 7% p =0.19). Of the 6 patients with known inflammatory bowel disease (IBD), 5 had an IgA greater than mean (mean 255, range 193-395) and one had an undetectable IgA. However of the 30 patients treated for H.pylori the mean IgA level was similar to the general population (mean 188, range 8-498).

More than 10% of patients with ITP have an elevated serum IgA. Subjects with IgA above mean are less likely to respond to standard treatment but more likely to respond to a splenectomy and more likely to have a major bleed than patients with an IgA below mean. This trend is more pronounced in elderly patients but was also suggested in patients younger than 65. However, those subjects with the highest IgA levels did not have a significantly increased risk of failing to respond to standard treatment and significant elevations in IgA were not obviously related to mucosal inflammation. Minor elevations in serum IgA may represent an inflammatory state not addressed with standard treatments for ITP. Further investigation into the role of IgA in the pathology of refractory ITP is warranted.

Bussel:Sysmex: Research Funding; Eisai, Inc: Research Funding; Ligand: Membership on an entity's Board of Directors or advisory committees, Research Funding; Immunomedics: Research Funding; Amgen: Equity Ownership, Membership on an entity's Board of Directors or advisory committees, Research Funding; Cangene: Research Funding; GlaxoSmithKline: Equity Ownership, Membership on an entity's Board of Directors or advisory committees, Research Funding; Genzyme: Research Funding; Scienta: Speakers Bureau; Shionogi: Membership on an entity's Board of Directors or advisory committees.