Lack of correlation between HLA-B35 resistance against herpes labialis and antibody titers to HSV-1 Giuseppe Gallina, MD, Vincenzo Cumbo, MD, Pietro Messina, MD, Vita Caprera. SD, Domenico Lio, MD, and Calogero Caruso, MD, Palermo, Italy INSTITUTE OF CLINICAL DENTISTRY AND INSTITUTE OF GENERAL PATHOLOGY UNIVERSITY OF PALERMO To investigate whether genetic factors linked to the human leukocyte antigens (HLA) might influence individual resistance to recurrent herpes labialis (RHL), we studied the frequencies of HLA-A, -B. and -C antigens in a sample of Sicilian population. The frequency of HLA-B35 was significantly decreased in the patient group 0, corrected = 0.018). Consequently, the relative risk of development of RHL in a subject positive for HLA-B35 was 20 times smaller than in a subject who does not bear B35. Furthermore, a study was made of the possible relationship between the presence of HLA-B35 antigen and antibody titers to herpes simplex virus type 1 (HSV-1) in 62 persons affected or not by RHL. Significantly elevated titers to HSV-1 were found in the diseased group @ < O.OOl), but the geometric mean of antibody titers in HLA-B35 positive subjects was not different from that of 835 negative subjects either of RHL-affected or in healthy persons. These data are in a good agreement with the hypothesis that humoral immune responses play a marginal role in the protection from HSV-1 recurrences. (ORAL SURC ORAL MED ORAL PATHOL 1989;68:167-70.1 H erpes simplex virus (HSV) infections are found worldwide, and seroepidemiologic surveys have dem- onstrated that more than 90% of persons, in the examined population, have antibody to HSV.‘,2 The recurrent herpetic perioral lesion (RHL), or “Herpes labialis,” is caused by herpes simplex virus type 1 (HSV-1). These lesions periodically occur in about 10% of persons and are characterized by recurrent vesicular eruptions of the lip.3 However, it is known that two types of clinically evident infec- tions can occur. The first is considered to be primary infection in a person without neutralizing antibodies, whereas the second is a recurrent infection in those having these antibodies. Furthermore, the clinical spectrum of HSV-1 infections varying by an unap- parent status of virus latency to an acute infectious disease, e.g., acute herpetic gingivostomatitis, or to recurrent infections suggests that individual host factors influence the natural history of the disease.4 It is also known that RHL occurs more frequently in relatives of patients than in the general population, This work was supported in part by grants from “Minister0 della Pubblica Istruzione-60% 1984, 1985, 1986 Universita di Paler- mo.” confirming the hypothesis that genetic factors may play a role in the pathogenesis of RHL.3 Human leukocyte antigens (HLA), coded by genes in the major histocompatibility complex (MHC) in human beings, have been identified as identical or closely linked to genes that may predispose toward or protect against some immunopathologic and infec- tious diseases.5 The possible relationship between class I (HLA-A, -B, -C) antigens and antibody titers to cytomegalovirus, measles, rotavirus, vaccinia, and varicella-zoster has been previously studied but the obtained results are rather inconclusive.6 In previous studies, we have demonstrated that in a Sicilian population, RHL showed a negative corre- lation with HLA-B35 antigen. These findings sug- gested that HLA-B35-linked gene(s) might influ- ence the individual resistance to herpetic recur- rences.7,8 Furthermore, Henrotte and coworkers9 recently reported that subjects positive for HLA-B35 showed light titers of postvaccinal anti-influenza antibodies. Therefore, the purpose of this study was to gain some insight into these questions by examining in our population, whether the observed resistance in HLA- B35 pos.itive subjects to RHL is linked to an increased antibody response to HSV- 1. 167