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Humoral autoimmunity has gained highest interest in neurology and psychiatry. Despite numerous recent articles on this hot topic, however, the biological significance of natural autoantibodies (AB) and the normal autoimmune repertoire of mammals remained quite obscure. AB may contribute to disorder-relevant phenotypes and are even believed to induce diseases themselves, but the circumstances under which AB become pathogenic are not fully understood. This review will focus on the highly frequent AB against the N-methyl-d-aspartate receptor 1 (NMDAR1-AB) as an illustrating example and provide a critical overview of current work (please note that the new nomenclature, GluN1, is disregarded here for consistency with the AB literature). In particular, it will demonstrate how little is known at this point and how many conclusions are drawn based on small numbers of individuals, fragmentary experimental approaches or missing controls.

Autoantibodies against N-methyl-d-aspartate receptor 1 in health and disease