Characterization of CD177‐reactive iso‐ and auto‐antibodies

Abstract

Background CD177 is a surface protein on neutrophils and a main mediator for the surface expression of proteinase 3 (PR3). Its functions are largely unknown. At least three types of antibodies have been described to target CD177: isoantibodies, which are formed in CD177‐null individuals as a result of an immune reaction following transfusion or pregnancy; autoantibodies present in sera from patients with autoimmune neutropenia; and antineutrophil cytoplasmic antibodies in sera from patients with glomerulonephritis with polyangiitis. In this study, we aimed to compare the binding characteristics of auto‐ and iso‐antibodies to optimize their detectability in the neutrophil serology laboratory. Study Design and Methods The reactivity of iso‐ and auto‐antibodies against CD177 was studied using granulocytes, “native” CD177/PR3 complex, and recombinant CD177 or PR3. Results All iso‐ and auto‐antibodies were reactive with CD177/PR3 when immobilized with monoclonal antibody (moab) 7D8. Seventy‐five percent of autoantibodies, but none of the isoantibodies, did not react with CD177/PR3 immobilized with moab MEM166. The majority of autoantibodies did not react with recombinant CD177, whereas most isoantibodies tested positive. Discussion Our results suggest that iso‐ and auto‐antibodies against CD177 target different epitopes. Isoantibodies mainly target CD177 alone, while the majority of autoantibodies target a native epitope present on the neutrophil surface, but absent from recombinant CD177 which lacks PR3. Moab MEM166 binds to the native epitope and hinders the binding of CD177 autoantibodies. The results may help to design diagnostic strategies, especially for the identification of autoantibodies.

Neutrophil-Specific Antigens: Immunobiology, Genetics and Roles in Clinical Disorders

“…Analysis has introduced an epitope formed by CD177/PR3 complex as a relevant epitope for CD177 autoantibodies but not isoantibodies. Interestingly this epitope is a signaling relevant epitope that upon binding of relevant antibodies induces neutrophil activation [63]. A previous study indicated CD177 as a heterophilic binding partner for platelet endothelial cell adhesion molecule 1 (PECAM-1).…”

Autoimmune Neutropenias: Update on Clinical and Biological Features in Children and Adults

“…For example, it is unknown if certain subpopulations of neutrophils are specific targets of immune mechanisms, for example, those expressing CD177 or those interacting with structures on endothelial cells significant for transmigration to the tissues or from the tissues back to PB or BM, and those interacting with organ-specific epitopes. 52 Likewise, it is unknown if there are recognition signals of neutrophil subpopulations for interaction with cytotoxic T-lymphocytes, NK cells, monocyte/macrophages, MDSC, and other cells that are involved in elimination or cross-talks with neutrophils. 15,17,39,45,53,54 Other possible mechanisms for AINP Cellular immune mechanism, implicating clonal or oligoclonal expansions of T-cell and NK-cell populations, may also account for NP particularly in adults.…”

An accurate genetic assay to identify human neutrophil antigen 2 deficiency

“…Accordingly, HNA‐2 null human subjects are prone to produce anti HNA‐2 isoantibodies. HNA‐2 isoantibodies are involved in a number of disorders such as neonatal alloimmune neutropenia, autoimmune neutropenia, drug‐induced immune neutropenia, and graft failure following marrow transplantation 6–10 . Additionally, HNA‐2 isoantibodies cause transfusion related acute lung injury (TRALI) and various pulmonary disorders 11–14 .…”

“…HNA-2 isoantibodies are involved in a number of disorders such as neonatal alloimmune neutropenia, autoimmune neutropenia, drug-induced immune neutropenia, and graft failure following marrow transplantation. [6][7][8][9][10] Additionally, HNA-2 isoantibodies cause transfusion related acute lung injury (TRALI) and various pulmonary disorders. [11][12][13][14] Consequently, HNA-2 is considered as one of the most important neutrophil antigens in human medicine.…”