The Allergic Bone Marrow? The Immuno-Capacity of the Human Bone Marrow in Context of Metal-Associated Hypersensitivity Reactions.

Melanie J Ort,Anastasia Rakow,Janosch Schoon,Sven Geissler

doi:10.3389/fimmu.2019.02232

Abstract

Arthroplasty ranks among the greatest achievements of surgical medicine, with total hip replacement termed “the operation of the century.” Despite its wide success, arthroplasty bears risks, such as local reactions to implant derived wear and corrosion products. Prevalence of allergies across Western society increases and along the number of reported hypersensitivity reactions to orthopedic implant materials. In this context the main focus is on delayed hypersensitivity (DTH). This mechanism is mainly attributed to T cells and an overreaction of the adaptive immune system. Arthroplasty implant materials are in direct contact with bone marrow (BM), which is discussed as a secondary lymphoid organ. However, the mechanisms of sensitization toward implant wear remain elusive. Nickel and cobalt ions can form haptens with native peptides to activate immune cell receptors and are therefore common T helper allergens in cutaneous DTH. The rising prevalence of metal-related allergy in the general population and evidence for the immune-modulating function of BM allow for the assumption hypersensitivity reactions could occur in peri-implant BM. There is evidence that pro-inflammatory factors released during DTH reactions enhance osteoclast activity and inhibit osteoblast function, an imbalance characteristic for osteolysis. Even though some mechanisms are understood, hypersensitivity has remained a diagnosis of exclusion. This review aims to summarize current views on the pathomechanism of DTH in arthroplasty with emphasis on BM and discusses recent advances and future directions for basic research and clinical diagnostics.

Highlights

T CELLS IN HUMAN BONE MARROWThe evolution of immune systems across the plant and animal kingdom has always been an arms race between pathogen and host
2% of the total lymphocyte numbers are circulating in the periphery compared to 11% residing in the bone marrow (BM), of which memory T cells constitute a major part [3, 4, 16, 22]
Allergy-related health care costs and the burden on patients suffering from any kind of overreaction of the immune system are already profound

Summary

Introduction

T CELLS IN HUMAN BONE MARROWThe evolution of immune systems across the plant and animal kingdom has always been an arms race between pathogen and host. Mechanisms to evade immune cells or to destroy an invader have been a fine tuned development over centuries [1] This lead to distinct lymphoid tissues in mammals, located at potential exposure sites such as skin, intestine, and pharynx. Implant components are usually composed of ceramics, polyethylene, metals, or metal alloys and sometimes fixed with bone cement. Some of these materials, especially nickel and cobalt, which are common allergens in cutaneous hypersensitivity [9, 10] have the capacity to trigger a hypersensitivity reaction or, more precisely, an allergic reaction and cause inflammation [11]. The aim of this review is to raise awareness that metal hypersensitivity might occur beyond the peri-implant membrane and the individual immunological memory has to be considered

Objectives

Findings

Conclusion