Eric L Greidinger1, Mark F Foecking, Sriya Ranatunga, Robert W Hoffman. 1. University of Missouri and Department of Veterans Affairs Medical Research Service, Harry S Truman Memorial Veterans Hospital, Columbia, Missouri, USA. greidingere@health.missouri.edu
Abstract
OBJECTIVE: To determine whether immune responses to an apoptotically modified form of a human lupus autoantigen can be distinguished from immune responses to the intact form of the same antigen. METHODS: Immunoblot and enzyme-linked immunosorbent assay techniques were used to test human autoimmune sera for the presence of antibodies to apoptotic forms of the U1- 70-kd small nuclear RNP antigen, while antibody recognition of intact U1-70 kd was blocked. RESULTS: poptosis-specific U1-70-kd antibodies were identified by immunoblot in 15 of 29 sera with antibodies to intact U1-70 kd and in 2 of 25 sera without measurable antibodies to intact U1-70 kd. Bacterially produced, purified, caspase-cleaved U1-70 kd without additional posttranslational modifications was a target of apoptosis-specific antibodies in 3 of 9 U1-70-kd-positive sera tested. CONCLUSION: The apoptotic form of U1-70 kd displays B cell epitopes that are not displayed on the intact form of U1-70 kd. Caspase cleavage in the absence of additional posttranslational modifications is sufficient to induce the display of some of these epitopes. Immunity to apoptotically modified proteins can develop against caspase-cleaved forms or against forms that undergo additional posttranslational modification.
OBJECTIVE: To determine whether immune responses to an apoptotically modified form of a human lupus autoantigen can be distinguished from immune responses to the intact form of the same antigen. METHODS: Immunoblot and enzyme-linked immunosorbent assay techniques were used to test human autoimmune sera for the presence of antibodies to apoptotic forms of the U1- 70-kd small nuclear RNP antigen, while antibody recognition of intact U1-70 kd was blocked. RESULTS: poptosis-specific U1-70-kd antibodies were identified by immunoblot in 15 of 29 sera with antibodies to intact U1-70 kd and in 2 of 25 sera without measurable antibodies to intact U1-70 kd. Bacterially produced, purified, caspase-cleaved U1-70 kd without additional posttranslational modifications was a target of apoptosis-specific antibodies in 3 of 9 U1-70-kd-positive sera tested. CONCLUSION: The apoptotic form of U1-70 kd displays B cell epitopes that are not displayed on the intact form of U1-70 kd. Caspase cleavage in the absence of additional posttranslational modifications is sufficient to induce the display of some of these epitopes. Immunity to apoptotically modified proteins can develop against caspase-cleaved forms or against forms that undergo additional posttranslational modification.
Authors: J A Somarelli; A Mesa; R Rodriguez; R Avellan; L Martinez; Y J Zang; E L Greidinger; R J Herrera Journal: Lupus Date: 2011-03 Impact factor: 2.911
Authors: M Huang; H Ida; M Kamachi; N Iwanaga; Y Izumi; F Tanaka; K Aratake; K Arima; M Tamai; A Hida; H Nakamura; T Origuchi; A Kawakami; N Ogawa; S Sugai; P J Utz; K Eguchi Journal: Clin Exp Immunol Date: 2005-10 Impact factor: 4.330
Authors: Robert W Hoffman; Tal Gazitt; Mark F Foecking; Robert A Ortmann; Michael Misfeldt; Rebecca Jorgenson; Steven L Young; Eric L Greidinger Journal: Arthritis Rheum Date: 2004-09