Deficiency of the specific granule proteins, R binder/transcobalamin I andlactoferrin, in plasma and saliva: A new disorder

The mechanisms of hereditary deficiency of R binder, which originates in ne utrophils and exocrine gland epithelium, are unknown and may be multiple. T his led us to examine if defective R binder synthesis also involves protein s that colocalize with it in neutrophil-specific granules and exocrine epit helial cells and may be under common regulatory control. Stored plasma and saliva samples from five unrelated R binder-deficient patients and control subjects were assayed for R binder, lactoferrin, cationic antimicrobial pro tein-is, neutrophil gelatinase-associated lipocalin, gelatinase, lysozyme, and myeloperoxidase, One patient, patient A, had lactoferrin levels below t he limits of detection in both plasma and saliva in addition to his R binde r deficiency. Although his deficiency involved lactoferrin as well, he had no history of predisposition to infection. PCR amplification of his R kinde r gene promoter region and the beginning of the first exon revealed no DNA abnormalities. His son and the son of his equally deficient brother, both p resumptive heterozygotes, had mild deficiency of both R binder and lactofer rin, The results show that R binder deficiency exists in at least two forms . One, presumably the less common of the two forms, is the new hereditary e ntity described here, which is characterized by deficiency of more than one specific granule protein in both plasma and saliva. Despite this more wide ly distributed absence of the proteins than is found in congenital specific granule deficiency, infection posed no clinical problem in the affected pa tient. (C) 2001 Wiley-Liss, Inc.