Some thoughts on the reproductive autoimmune failure syndrome (RAFS) and Th-1 versus Th-2 immune responses

PROBLEM: The concept of immunologically induced reproductive failure has remained very controversial. Especially the question whether abnormal immune function can cause infertility has recently been subject to strong disagreement. This opinion piece is an attempt to reconcile difference of opinion by integrating clinical data from the human experience with well-established experimental models in animals. METHOD OF STUDY: Review of published literature. RESULTS: Experimental animal data, especially in the mouse, have suggested that normal pregnancy requires a switch to an immune response with T helper (Th)-2 preponderance. Recent data from the human experience suggest that infertility, repeated pregnancy loss and certain complications of pregnancy may be the consequence of abnormal Th-1 preponderance. In analogy, to animal models, immunologic reproductive failure in humans, may therefore not be the consequence of specific autoantibody abnormalities or natural killer (NK)-cell abnormalities, but the reflection of a misdirection of a more broadly based immune response. CONCLUSIONS: Under such a model, both diagnosis and treatment of immunologically induced forms of reproductive failure require re-evaluation. Such a model, however, provides a satisfactory explanation for contradictory findings in the human experience that have led to strong disagreements among investigations.