Discussion. Paper # 096

Paper # 096

Thymic microenvironmental changes in human congenital syphilis

Eliene C. Fonseca, Mônica P. Almeida, Évlin H. Maia, Dora M. F. Menezes and Wilson Savino*

[Title] [Introduction] [Materials and Methods] [Results] [Pictures] [Bibliography]

DISCUSSION

The present investigation corresponds to the first systematic survey on the thymic microenvironment from patients bearing congenital syphilis. In particular, we focused herein the extracellular matrix components of the thymic microenvironmental compartment. Regarding this respect, several aspects merit discussion.

One of the most striking thymic ECM changes in CS is represented by the extremely thickened connective tissue septa. Actually, they are alt least tem-fold thicker as compared to age-matched normal thymuses. Yet, such abnormality is not thymus specific, and most likely corresponds to a general feature of the disease.

Thymic extramedullary hematopoiesis mainly in thickened septa must be na exacerbation of GM-CSF production by thymic epithelial cells (19).

Intralobular ECM-containing networks and high numbers of B lymphocytes and immunoglobulins bound to ECM structures can be found in CS and thymus of myastenia gravis, an autoimmune related disease. A cortical ECM network was also observed in thymuses from Down’s syndrome (12).

Besides the alterations of ECM components in CS, we detected high amounts of immunoglobulins directly bound to thymic ECM-containg structures, particularly basement membrane, as well as we observed in Down’s syndrome (12).

Taken together, these findings suggest that abnormal ECM containing networks may be associated with pathological B and/or T lymphocyte migration within the thymus and its parallelism with thymocyte death is totally clear.

Expression of basement membrane proteins, namely type IV and III collagen, laminin and fibronectin is dramatically increased in atrophic thymuses. Thus, in a variety of experimental and human infections resulting in severe thymocyte depletion, na important intralobular, ECM-containing network was conssistantly observed, as in murine rabbies, acute experimental Chagas’ disease, scistossomiasis as well as congenital cytomegalovirus and postnatal measles infection (33).

Kinetic studies in both hydrocortizone, T. cruzi and S. mansoni in vivo models revealed that such increase in ECM production actually preceeds thymocyte depletion. These data together with our findings that fibronectin enhance thymocyte death in vitro raised the hypothesis that the increase in thymic extracellular matrix occurring as a general feature in acute infectious diseases may be somewhat related to thymocyte death (32, 34, 42).

CONCLUSIONS:

There is a direct correlation between the lymphocyte depletion degree and the increase in ECM intralobular network. This one, lymphocyte traffic and cellular interactions can interfere in selection of T cell repertoire.
The presence of autoantibodies anti-ECM can be envolved in genesis and/or manteinance of the found alterations.
Thymus must be considered a target organ also in congenital syphilis, what can be interesting for immunorregulatory terapies that can contribute to make better the surveillance of affected neonates and infants.