Abstract
BackgroundThe aim of this study was to determine the presence and the intensity of humoral immunity to melanoma-associated antigens: tyrosinase and melanin, in patients with melanoma, in persons with vitiligo and in control healthy people.MethodsThe study involved 63 patients with melanoma and 19 persons with vitiligo. Control group consisted up to 41 healthy volunteers. Mushroom tyrosinase and synthetic melanin were used as the antigens.ResultsELISA test showed significantly (p < 0.0000004 and p < 0.04) lower levels of IgM anti-tyrosinase autoantibodies, in melanoma and vitiligo patients respectively, compared to controls.Although there was no significant difference between the levels of IgA anti-melanin autoantibodies in melanoma or vitiligo patients in comparison with controls, the enhanced concentrations of anti-melanin IgA autoantibodies were preferentially found in melanoma patients with metastatic disease. Significantly high percentage in the Fc alphaRI (CD89) positive cells was determined in melanoma patients (p < 0.002 and p < 0.008) in comparison to that found in healthy people or in patients with vitiligo, in the already mentioned order, pointing that IgA dependent cellular cytotoxicity is not important for the immune action against melanoma, even more that it is included in some immune suppression.Levels of IgG autoantibodies to mentioned antigens in melanoma patients although low were not significantly lower from controls. These findings analyzed together with the statistically significant low percentage of FcgammaRIII, (CD16) positive immunocompetent cells (p < 0.0007 and p < 0.003), which was found in patients with melanoma compared with healthy or vitiligo people respectively, and statistically significant low percentage of (CD16 + CD56+) natural killer (NK) cells (p < 0.005) found in melanoma patients in comparison to healthy controls pointed to the low probability for anti-melanoma IgG mediated, antibody mediated cellular cytotoxicity, (ADCC) and NK cytotoxicity. Moreover the ratio of the percentages of granulocytes and percentage of lymphocytes was statistically higher in patients with melanoma in relation to healthy people as well as to people with vitiligo (p < 0.0007 and p < 0.05 respectively).ConclusionAutoantibodies to tyrosinase and to melanin which are found even in healthy people, point that consummation of edible mushrooms that carry the antigen tyrosinase and melanin, could influence the humoral anti-melanoma immune response.Levels of different immunoglobulin classes of anti-melanin and anti-tyrosinase antibodies varied depending on the presence and the stage of studied diseases. Besides, the statistically enhanced ratio of the percentages of granulocytes and percentage of lymphocytes, together with statistically decreased percentage of NK cells is found in analyzed melanoma patients.
Highlights
The aim of this study was to determine the presence and the intensity of humoral immunity to melanoma-associated antigens: tyrosinase and melanin, in patients with melanoma, in persons with vitiligo and in control healthy people
Melanoma is very serious disease and it is important, to emphasize, to not overlook, that very recently, some new immunotherapy approaches for suppression of metastatic melanoma showed great achievement. These are: autologous TILs administered in conjunction with interleukin-2 following a lymphodepleting preparative regimen [4,9], while the others are based on the enhancement of the immune system function by blockade of the cytotoxic Tlymphocyte associated antigen-4 (CTLA-4) by the monoclonal antibody ipilimumab which is at the present approved by the United States Food and Drug Administration (FDA) for use in patients with unresectable melanoma [6,7,10]
The significantly lower levels of IgM anti-tyrosinase autoantibodies are found in melanoma patients and in people with vitiligo, in comparison to that found in controls p < 0.0000004 and p < 0.04 respectively, as seen on Figure 1. ( 24 out from 28 melanoma patients which had decreased anti-tyrosinase IgM autoantibodies had metastatic disease as seen on Table 1 and Figure 1.)
Summary
The aim of this study was to determine the presence and the intensity of humoral immunity to melanoma-associated antigens: tyrosinase and melanin, in patients with melanoma, in persons with vitiligo and in control healthy people. Melanoma is very serious disease and it is important, to emphasize, to not overlook, that very recently, some new immunotherapy approaches for suppression of metastatic melanoma showed great achievement These are: autologous TILs administered in conjunction with interleukin-2 following a lymphodepleting preparative regimen [4,9], while the others are based on the enhancement of the immune system function by blockade of the cytotoxic Tlymphocyte associated antigen-4 (CTLA-4) by the monoclonal antibody ipilimumab which is at the present approved by the United States Food and Drug Administration (FDA) for use in patients with unresectable melanoma [6,7,10]. New biological agents designed to block oncogenic signal transduction such is vemurafenib inhibiting v-Raf murine sarcoma viral oncogene homologue B1 is active only in melanoma patients with tumor cells harboring BRAF mutations It is considered for the therapy of melanoma alone as well as in combination with peptide vaccines or with ipilimumab, or with dacarbazine [11]. It is important to note that immunologically opposite disease, vitiligo, (a dermatological disorder characterized by the loss of melanin, which results in depigmented areas of the skin), appears in many cases of melanoma regression [13,14]
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