Comparative Analysis of Serological Markers of Herpes Viruses and Hypergammaglobulinaemia in Patients with Angioimmunoblastic T-Cell Lymphoma

Abstract

Introduction: Angioimmunoblastic T-cell lymphoma (AITL) is a peripheral T-cell lymphoma characterized by generalized lymphadenopathy, hepatosplenomegaly and dysproteinemia. Some believe that AITL is associated with herpes viruses, especially Epstein-Barr virus (EBV). It has been speculated that herpes viruses can directly or indirectly trigger this disorder and induce abnormal hyperimmune reaction, manifested by hypergammaglobulinaemia in 50-83% pts. So antiviral antibodies, mainly anti-EBV, are suggested as hypergammaglobulinaemia substrate.Aim: The aim of the study was to compare serological markers of herpes viruses and gammapathy presence in patients at the onset of AITL.Patients and methods: 25 patients with AITL were enrolled in the study, the male/female ratio was 16/9; median age was 63 (29-81) years. Diagnosis AITL was based on standard WHO criteria. Antiviral antibodies against human cytomegalovirus (HCMV), Epstein-Barr virus (EBV) and Herpes simplex virus types 1 and 2 (HSV 1, 2) were investigated: IgM and IgG titers were tested in ELISA. Titer of anti-HCMV-IgG and anti-HSV 1, 2 IgG corresponding to a dilution of 1:3200 and further was considered as high. Concentration of anti-EBNA-1-IgG 60 c.u. (conventional units) and more was considered as high. Immunochemical studies of blood serum included serum protein electrophoresis/immunofixation, nephelometric quantification of total immunoglobulins, serum free light chain assay.Results: Polyclonal hypergammaglobulinaemia was revealed in 14 (56%) of 25 pts: 10 cases of polyclonal IgG and 10 cases of polyclonal IgM hypergammaglobulinaemia (6 pts had IgM and IgG hypergammaglobulinaemia simultaneously). Hypogammaglobulinaemia was detected in 8 (15%) of 25 cases: decreased level of IgG was observed in 8 pts, IgM - in 4 pts. Serological markers of active herpes virus infections (antiviral IgM) were found in 13 (52%) of 25 pts: anti-EBV-IgM was detected only in 3 (12%) cases, anti-HSV 1, 2 IgM - in 10 (40%) of 25 cases and anti-HCMV-IgM - in 4 (16%) cases. Two patients had antiviral IgM against 2 viruses and 1 patient against 3 viruses simultaneously. So the anti-HSV 1,2 IgM not anti-EBV-IgM demonstrated the highest detection rate unexpectedly. Increased level of antiviral IgG was determined in 21 (84%) of 25 pts. Increased concentration (65 and more c.u.) of anti-EBNA-1-IgG was revealed in 16 (64%) cases, elevated titer of anti-HSV 1, 2 IgG - in 19 (76%) of 25 pts, excessed level of anti-HCMV IgG was observed in 6 pts. Thus, HSV 1,2 turned out to be the most frequent cause of antiviral IgG increased level.A comparison of immunochemical and virological data was carried out. Antiviral IgM was detected in 10 out of 10 cases with polyclonal IgM hypergammaglobulinaemia (9 were anti-HSV 1,2-IgM positive). The rest 3 antiviral IgM positive patients showed no signs of polyclonal IgM exceeding the reference values (Table 1). There wasn't a case of polyclonal IgM hypergammaglobulinaemia without antiviral IgM, what are points out to a strong correlation (p=0.021).Elevated level of antiviral IgG was detected in 8 out of 10 (80%) cases of polyclonal IgG hypergammaglobulinaemia (Table 2). Two cases of polyclonal IgG hypergammaglobulinaemia were not accompanied by an increased level of antiviral IgG, and on the contrary 7 out of 8 (75%) cases of hypogammaglobulinaemia were accompanied by an excess of antiviral IgG (mostly due to EBV and HSV 1, 2). Thus, there was no correlation between polyclonal IgG hypergammaglobulinaemia and antiviral IgG elevation (0.366<p<0.975).Conclusion: No evidence of contribution of herpes virus-induced humoral responce to polyclonal hypergammaglobulinaemia class G was observed (0.366<p<0.975). In cases with polyclonal hypergammaglobulinaemia class M, on the contrary, the connection could be suspected. It seems that HSV 1, 2 induces the maximum contribution to the hypergammaglobulinaemia class M [Display omitted] DisclosuresNo relevant conflicts of interest to declare.