In unserer prospektiven Pilotstudie konnten wir zeigen, dass Patienten mit rezidivierenden Infekten der Atemwege im Vergleich zu einer gesunden Kontrollgruppe eine verminderte IgA-Sekretion im Speichel aufweisen. Die absoluten sIgA-Konzentrationen im Speichel unterschieden sich zwischen den beiden Gruppen nicht signifikant, da diese starken intra- und interindividuellen Schwankungen unterliegen, welche durch die Bildung von sIgA/Albumin-Quotienten ausgeglichen werden können. So waren die sIgA/Albumin-Quotienten der Patientengruppe signifikant niedriger als die der Kontrollgruppe und wurden nicht durch Alter oder Geschlecht beeinflusst. Proben der Patientengruppe, in welchen Albumin nachgewiesen werden konnte, waren doppelt so häufig sIgA-negativ wie Proben der Kontrollgruppe.
Die sIgA/Albumin-Quotienten korrelierten in der Patientengruppe signifikant mit IgA und den IgA-Subklassen im Serum, am stärksten mit IgA2. Zudem wiesen alle Patienten mit serologisch erniedrigtem IgA2 auch eine fehlende Sekretion von sIgA im Speichel auf.
Dies spiegelt die Bedeutung der IgA2-Subklasse in sekretorischem IgA wieder, wo sie, im Gegensatz zu systemischem IgA, die dominante Subklasse darstellt.20 IgA und seine Subklassen im Serum zeigten untereinander eine stärkere Korrelation als mit den erhobenen sIgA/Albumin-Quotienten, da systemisches und sekretorisches IgA von unterschiedlichen B-Zell-Populationen gebildet werden.20 Diese Beobachtung zeigt die begrenzte klinische Aussagekraft systemischer IgA-Werte in Bezug auf rezidivierende Infektionen der Atemwege.
IgG2 und IgG4 sind im Speichel durchschnittlich überrepräsentiert113. In unserer Studie korrelierten sie signifikant mit IgA im Serum. Bereits vorherige Studien zeigten diesen Zusammenhang zwischen IgA, Ig2, Ig4 und Infektanfälligkeit.67,114,116 Somit scheinen diese Subklassen ebenfalls eine Rolle in der Pathogenese von rezidivierenden Infektionen der Atemwege zu spielen. Insbesondere bei Patienten mit beeinträchtigter IgA-Produktion beeinflussen IgG2 und IgG4 Frequenz und Schwere der Infektionen und sollten immer miterhoben werden.115,117
53
Auch Patienten mit normalen Immunglobulinen im Serum zeigten im Vergleich zur Kontrollgruppe signifikant niedrigere sIgA/Albumin-Quotienten. Insbesondere diese Patientengruppe, bei der serologisch keine Auffälligkeit der Immunglobulinproduktion nachgewiesen werden kann, könnte von der Erhebung sekretorischer Immunmarker diagnostisch profitieren. SIgA/Albumin-Quotienten scheinen unseren Ergebnissen nach, durch ihre geringere inter- und intraindividuelle Variabilität, dazu besser geeignet zu sein als absolute sIgA-Konzentrationen im Speichel. Basierend auf unseren Ergebnissen erscheint es diagnostisch sinnvoll, neben dem Gesamt-IgA im Serum auch die IgA- und IgG-Subklassen zu bestimmen, da diese ebenfalls Rückschlüsse auf die sekretorische Immunität zulassen.
Bevor der sIgA/Albumin-Quotient Eingang in die Routinediagnostik finden kann, werden größere Studien benötigt, um die vorliegenden Daten zu verifizieren und gegebenenfalls den Einfluss weiterer individueller oder Umwelt-Faktoren auf die Produktion sekretorischer Immunglobuline zu untersuchen. Um eine Vergleichbarkeit von Studien zu gewährleisten und um Referenzwerte zu etablieren müssen Speichelentnahme, Messmethode und Entnahmezeitpunkt standarisiert werden. Ebenso müssen ausreichend sensitive Assays für sIgA und Albumin angewendet werden, um für jede Probe einen sIgA/Albumin-Quotienten berechnen zu können. Gelingt dies, könnte in Zukunft die Diagnostik bei rezidivierenden Infektionen, ergänzend zur aktuell im Fokus stehenden systemisch-serologischen Diagnostik, um die Dimension der sekretorischen Immunglobuline ergänzt werden.
54
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