Anti-NCF1 (aa 378-390) polyclonal antibody

Introduction: Immune responses against collagen type II (CII) are crucial for the development of collagen-induced arthritis (CIA). The aim of the present study was to evaluate and compare the CII-directed T cell and antibody specificity at different time points in the course of CIA using two mouse strains on the B10 genetic background B10. Q, expressing A(q) MHC class II molecules, and B10.DR4.Ncf1*(/)*, expressing human rheumatoid arthritis-associated MHC II DR4 molecules (DRA*0101/DRB*0401). Methods: B10. Q and B10.DR4.Ncf1*(/)* mice were immunized with CII emulsified in adjuvant and development of CIA was assessed. T cells from draining lymph nodes were restimulated in vitro with CII peptides and interferongamma (IFN-gamma) levels in culture supernatants were evaluated by ELISA. CII-specific antibody levels in serum samples were measured by ELISA. Results: At four different CIA time points we analyzed T cell specificity to the immunodominant CII epitope 259273 (CII259-273) and several posttranslationally modified forms of CII259-273 as well as antibody responses to three B cell immunodominant epitopes on CII (C1, U1, J1). Our data show that CII-specific T and B cell responses increase dramatically after disease onset in both strains and are sustained during the disease course. Concerning anti-CII antibody fine specificity, during all investigated stages of CIA the B10. Q mice responded predominantly to the C1 epitope, whereas the B10.DR4.Ncf1*(/)* mice also recognized the U1 epitope. In the established disease phase, T cell reactivity toward the galactosylated CII259-273 peptide was similar between the DR4- and the A(q)- expressing strains whereas the response to the non-modified CII peptide was dramatically enhanced in the DR4 mice compared with the B10. Q. In addition, we show that the difference in the transgenic DR4-restricted T cell specificity to CII259-273 is not dependent on the degree of glycosylation of the collagen used for immunization. Conclusions: The present study provides important evaluation of CII-specific immune responses at different phases during CIA development as well as a comparative analysis between two CIA mouse models. We indicate significant differences in CII T cell and antibody specificities between the two strains and highlight a need for improved humanized B10. DR4 mouse model for rheumatoid arthritis.

Purpose of review Chronic granulomatous disease (CGD) is a primary immunodeficiency, with a defect of phagocytes in killing specific pathogens. CGD is characterized by severe recurrent bacterial and fungal infections and dysregulated inflammatory response. Since its first description as fatal disease about 60 years ago, a significant improvement in outcome has been achieved in the last 20 years. The purpose of this review is to framework recent advances in CGD immunopathogenesis, management of disease manifestation and cure of CGD patients. Recent findings For years, CGD is a known cause of life-threatening infections and excessive inflammation. The cause and the management of inflammatory reactions, however, have not been clarified, and the range of clinical presentation is growing with corresponding novel therapeutic interventions. Recent work focuses on the best outcome of hematopoietic stem cell transplantation (HSCT) and gene therapy for the cure of CGD patients, more specifically, those with X-linked and p47(phox) mutations. Summary The genetics and phenotype of CGD is well characterized; however, the underlying mechanisms, the treatment of its inflammatory manifestations and the cure of CGD is under further investigation.