Tuftsin Deficiency

Tuftsin, which is derived from the heavy chain of human immunoglobulin, is a tetrapeptide (Thr--Lys--Pro--Arg) that stimulates the phagocytic activity of polymorphonuclear leukocytes. (Tuftsin was named for Tufts University where the tetrapeptide was discovered.) It is activated in the spleen and bound to a carrier leukokinin molecule, a gamma-globulin which coats the polymorph. Tuftsin is absent in splenectomized humans and dogs. Its absence after splenectomy leads to problems with infection. Congenital familial deficiency of tuftsin with a history of repeated and severe infections has been observed in at least 4 families (Constantopoulos and Najjar, 1973; Najjar, 1981). In each of the 2 families reported by Constantopoulos et al. (1972), 1 child had recurrent infections and 1 parent had low tuftsin levels but was asymptomatic. Constantopoulos et al. (1972) observed affected father and son. In 1 patient, a mutant peptide was identified as Thr-Glu-Pro-Arg, representing a transition mutation (A-to-G) such that AAA or AAG = lysine is converted to GAA or GAG = glutamic acid (Konopinska et al., 1981). Bump et al. (1986) isolated the tuftsin receptor. Najjar (1987) indicated that in all instances only 1 parent of tuftsin-deficient individuals has also been deficient and that in no instances have both parents been normal. It is noteworthy that although this seems to be an autosomal dominant trait, the deficiency is complete. This suggests that allelic exclusion may be operative. Some of the tuftsin deficiency cases, which in Najjar's experience total 20, have been discovered as a result of studying patients with recurrent infections in whom no immune abnormality could be demonstrated, but in whom gamma globulin, administered for lack of anything else to do, resulted in great benefit (Najjar, 1987). Cases have been reported in Japan. In attempts to produce an antibody against tuftsin for diagnostic use, Naim et al. (1989) found that tuftsin appears to be nonantigenic to mammals even when coupled to various carrier proteins. Thus, the only reliable analytical assays are physical methods such as RP-HPLC and mass spectrometry.