Antikörper gegen humane Leukozytenantigene (HLA) bei männlichen Apheresespendern ohne klassische Alloimmunisierung

Zusammenfassung

Im Rahmen von Präventivmaßnahmen zur Vermeidung von TRALI (transfusionsassoziierte akute Lungeninsuffizienz) wurden in einer Studie 15 523 männliche und weibliche Apheresespenderinnen und -spender mit und ohne positiver Immunisierungsanamnese (IA) auf HLA-Klasse-I-, HLA-Klasse-II- und HNA-Antikörper (AK) untersucht. Unsere Ergebnisse zeigten, dass bei 3,85% der männlichen Spender ohne IA HLA-AK und bei 0,10% HNA-AK auftraten. Diese Beobachtung stellt die seit Beginn der HLA-Ära vor 50 Jahren klar bewiesene Aussage infrage, dass HLA-AK nur durch eine Alloimmunisierung infolge von Schwangerschaften, Transfusionen oder Transplantationen entstehen können. Wir diskutieren mehrere mögliche Kausalitäten dieser positiven Reaktionen:

1. Sind es natürliche AK, die gegen gemeinsame Antigenstrukturen auf endo- und exogenen Peptiden, z. B. von Mikroben oder Pilzen, aufgenommenen Lebensmitteln oder inhalierten Allergenen, gerichtet sind?

2. Sind es Allo-AK, die im Zusammenhang mit möglichen Immunisierungsereignissen, z. B. einer Impfung, entstanden sind?

3. Sind andere Alloimmunisierungsereignisse möglich?

4. Handelt es sich um falsch positive Reaktionen, die im LABScreen Multi durch einen zu niedrig festgelegten positiven Cut-off bestimmt wurden?

Große Aufmerksamkeit richteten wir auf den Ausschluss möglicher falsch positiver Reaktionen, da der LABScreen Multi als höchst sensitiv eingeschätzt wird. Nach Validierung eines neuen positiven Normalized-Background-Cut-offs (NBG: Normalized Background) und der Nachtestung von Rückstellproben der als positiv getesteten männlichen Spender konnten 50% der HLA-Klasse-I- und 43% der HLA-Klasse-II-AK nicht bestätigt werden. Dennoch blieben 1,5% der getesteten männlichen Spender für HLA-Klasse I und 0,5% für HLA-Klasse II positiv. Handelt es sich hier ausschließlich um HLA-spezifische oder um heterophile AK? Welche klinische Bedeutung haben diese AK bei der Prävalenz von TRALI oder für die Transplantationsimmunologie?

Abstract

In order to reduce the risk of TRALI (transfusion-related acute lung injury) 15 523 male and female apheresis donors with and without immunization history were tested for HLA class I, HLA class II and HNA antibodies (Ab). Our results showed that 3.85% of the male donors without immunization history were positive for HLA Ab and 0.10% for HNA Ab. This observation calls into question the statement, which has been clearly proven since the beginning of the HLA era 50 years ago, that HLA Ab can only be produced through alloimmunization as a result of pregnancy, transfusion or transplantation. We discuss several possible causalities of these positive reactions for HLA Ab:

1. Are there natural antibodies against common antigen structures on endo- and exogenous peptides, e. g. of microbes or fungi, ingested food or inhaled allergens?

2. Are there alloantibodies related to possible potential immunization events such as vaccination?

3. Are other alloimmunization events possible?

4. Are these false positive reactions that were determined in the LABScreen Multi by a positive cutoff set too low?

We set special attention to the exclusion of possible false positive reactions as the LABScreen Multi assay is considered highly sensitive. After validating a new positive NBG cutoff and retesting of reserve samples from the donors tested as positive, 50% of HLA class I and 43% of HLA class II Ab could not be confirmed. Nevertheless, 1.5% of the male donors tested remained positive for HLA class I and 0.5% for HLA class II. Are these only HLA-specific or heterophilic Ab? What is the clinical significance of these Ab in order to prevent TRALI or for transplantation immunology?

Schlüsselwörter

HLA-/HNA-Antikörper - TRALI-Präventivmaßnahmen - LABScreen Multi - heterophile Antikörper - Epitope

Key words

HLA/HNA antibodies - TRALI preventive measures - LABScreen Multi - heterophilic antibodies - epitopes

Publication History

Article published online:
16 November 2020

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