THE APPEARANCE OF AUTOIMMUNE PHENOMENA DURING POST-BURN THERAPY

D'Arpa W, Masellis M., Lio R*., Pipitone G.

Divisione Chir. Plastica, Ospedale Civico USL 58, Palermo, Italia
* Servizio Pat. Clinica, Ospedale Ingrassia USL 59, Palermo

SUMMARY. The literature offers numerous data indicating that the bum trauma causes a serious immune deficiency which profoundly affects the natural progress of the lesion. It is not however so well known if the imbalance of the immune system in such patients provokes the disappearance of autoimmune phenomena. This work assesses the appearance of organ specific and non-specific autoantibodies at different times after the bum lesion. It was found that anti-epithelial cell antibodies appeared rather late in 60% of the patients. This finding may account for some of the late complications of the -bum syndrome".

Introduction

The burn trauma induces a severe immunesuppression that involves T lymphocyte functions with damage to both cellular (1) and T dependent humoral immune responses (2).
There is also profound but limited reduction of circulating immunoglobulin levels that are restored at the latest on day 7 post-burn.
Despite the general immune depression induced, in the burn syndrome the production was observed of autoantibodies (autoAB) (2) that can play a role in the evolution of the natural history of the lesion.
Data reported in the present paper show that in a group of pAtients with 11 or III degree lesions extending to over 30% of total surface body area both organ and non organ specific autoAB are produced.
Some autoAB seem to be involved in the alterations of repairing processes that can be observed in the chronic phases of the bum syndrome.

Materials and methods

Patients

Blood samples were obtained from 20 patients affected by burns of 2nd or 3rd degree extending to over 30% TI1SA.
Autoantibody detection
The rheumatic factor (RF) was measured using an ICS 11 nephelometer system (Beckman) that relates the RF levels with the light scattering obtained.
Anti-cardiolipin antibodies (ACA) were detected by an enzymatic immunoassay. Sera were incubated with antigen coated plates at 37' C for two hours;,the rinsed plates were then incubated with anti-human immunoglobulins conjugated with peroxidase for one hour at 37' C and finally with OPD substrate for 30 min at room temperature. The absorbance increase was related to the ACA concentration.
The presence of the other organ and non-organ specific antibodies was evaluated by the indirect immunofluorescence technique.

Results and discussion

Table I shows the non-organ specific autoAb pattern in a group of burned patients with 11 and III degree lesions extending to over 30% TBSA 4, 10, 20 and 30 days after trauma.
The appearance of autoAb is detectable as early as day 10 with a peak at day 20.
The major frequencies of positivities are linked to the anti-immunoglobulin (rheumatic factor, RF) and anti-phospholipid antibodies (anti-cardiolipin antibodies, ACA) that are frequently observed in the autoimmune diseases. These antibodies occur in a variety of acute and chronic diseases, but usually disappear with resolution of the disease (3).
However, as ACA are involved in the antisyphilis response, the nonspecificity of the antibody response detected in bum patients was controlled by the indirect immunofluorescence assay with fixed treponema antigens (data not shown).
These results suggest that the burn trauma induces a nonspecific production of autoantibodies, probably linked to the well-known phenomenon of the polyclonal activation of B lymphocytes by cellular or bacterial endotoxin that can occur in bum trauma (4).
This view is strengthened by the appearance in the early phases of some organ specific autoantibodies such as APCN and ASMA (Table 2). One can also speculate about the role that the production of these autoAb, together with the hyperstimulation of the hypothalamic-adrenal axis by trauma (5), could play in the pathogenesis of the gastric haemorrhagic lesions by stress.

Significant positivity frequencies by chi-square test with Yates' correction. The data reported in Table 2 show that sera in about 50% of the patients at day 10 and in over 70% at day 20 were positive for the anti-skin antibodies (ASA).
These autoAb are specific for the basal membrane or the cells of the basal stratum of the epidermis and are frequently associated with the bullous pemphigoid autoimmune disease (6).
Our data suggest that the increase of frequency of these autoAb in burn patients during the time course of post-burn recovery is linked to the skin autoantigen release induced by burn trauma. Thus, in agreement with the current views on the role of autoAb production during several non autoimmune diseases (7), we feel that they could play a role in the clearance of the large amounts of the skin autoantigens produced.
In contrast, in a small group of patients who had the highest ASA titers, we observed a l,ate skin repair with a significantly prolonged time of recovery. This latter result suggests that, in some conditions, the evaluation of the titers of anti-skin antibody could be considered another additional criterion for the prognosis of the chronic burn syndrome.
However, our data suggest that the autoimmune antibody production observed in our patients could be regarded as another expression of the severe impairment that burn trauma induces in the homeostasis of the immune system.

RÉSUMÉ. Il y a dans la littérature beaucoup de données qui indiquent que le traumatisme thermique induit un immunodéficit grave qui conditionne profondement l'histoire naturelle de la lésion (Ninneman et al., 1985). Cependant on ne sait pas avec autant de certitude si le déséquilibre du système immun chez ces patients cause la disparition des phénomènes autoimmuns. Cette recherche évalue l'apparition des auto-anticorps organe et non-organe spécifiques, à divers moments après la lésion. Les résultats démontrent que des anticorps anti-cellules épithéliales apparaissent surtout tardivement chez 60% des patients. Cette découverte peut expliquer quelques complications tardives du "syndrome de brûlure".

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