Secondary Syphilis in Persons Infected With and Not Infected With HIV-1

Abstract

To better understand the cutaneous immune response to Treponema pallidum, we performed an immunohistologic study of skin biopsies from a total of 11 patients with secondary syphilis; biopsies from five persons infected with HIV-1 were included in the analysis to assess at the tissue level the impact of concomitant HIV-1 infection on disease expression. In all of the biopsies, staining for HLA-DR, a marker for cellular activation, was observed among infiltrating leukocytes, dermal vascular endothelial cells, and keratinocytes. Infiltrating mononuclear cells stained positively for CD4 or CD8, with CD4+ cells always being in the majority. Surprisingly, most of the CD4+ cells had histiocytic, rather than lymphocytic, morphologic characteristics. Immunostaining for CD14 confirmed that these cells were monocytic in origin, whereas immunostaining for CD3 revealed that the lymphocytes were predominantly CD8+ cytotoxic T cells. B cells were not detected despite the presence of variable numbers of plasma cells in all specimens. By immunofluorescence, all of the specimens demonstrated perivascular deposition of immunoglobulins, complement, or fibrinogen; linear staining at the dermal-epidermal junction also was observed in most of the specimens. No differences in immunocytochemical or immunofluorescence staining patterns were observed between the specimens from patients who were HIV positive and patients who were HIV negative. In addition to providing a more precise definition of the infiltrating cells in syphilitic lesions, our results, taken as a whole, indicate that cellular immune processes are largely responsible for the development of cutaneous manifestations during syphilitic infection and that coinfection with HIV-1 has little discernible effect on the cutaneous response to T. pallidum.

The Cutaneous Response in Humans toTreponema pallidumLipoprotein Analogues Involves Cellular Elements of Both Innate and Adaptive Immunity

“…In keeping with this idea, we found that there was indeed overlap between the cellular response to the lipopeptides and the elements that comprise the infiltrates of early syphilis lesions. A prominent example was the marked enrichment for macrophages in the blister fluids, a finding that parallels immunohistochemical analyses showing that activated macrophages are the predominant mononuclear cell in secondary syphilis lesions (4). Lymphocytes are a nearly ubiquitous component of early syphilis lesions (1,5) and were readily identified in blister fluids.…”

“…On the one hand, they cause the tissue damage that ultimately gives rise to clinical manifestations, while on the other, they also are responsible for the clearance of treponemes, a prerequisite for lesion resolution (2,3). Cellular infiltrates composed of T lymphocytes, macrophages, and plasma cells are the sine qua non of syphilitic lesions (1)(2)(3)(4)(5)(6)(7). Immunocytochemical and RT-PCR analyses of early syphilitic skin lesions have revealed that these infiltrating cells, as well as keratinocytes and proximal vascular endothelium, are activated and that the T cells are elaborating cytokines consistent with a Th1 response (4,8).…”

“…Cellular infiltrates composed of T lymphocytes, macrophages, and plasma cells are the sine qua non of syphilitic lesions (1)(2)(3)(4)(5)(6)(7). Immunocytochemical and RT-PCR analyses of early syphilitic skin lesions have revealed that these infiltrating cells, as well as keratinocytes and proximal vascular endothelium, are activated and that the T cells are elaborating cytokines consistent with a Th1 response (4,8). Because macrophages are both professional phagocytes and a rich source of proinflammatory mediators, their presence in large numbers is thought to be central to both lesion formation and resolution (2,4,6).…”

“…Whole blood was either treated with erythrocyte lysis buffer (150 mM NH 4 Cl, 1 mM KHCO 3 , and 1 mM EDTA) to produce erythrocyte-depleted leukocytes or centrifuged in Vacutainer Cell Preparation Tubes (Becton Dickinson, Franklin Lakes, NJ) to isolate PBMCs. Blister fluids were transferred to 3 ml of fluorescence assay (FA) buffer (Difco Laboratories, Detroit, MI) containing 2 mM EDTA (pH 8) and washed once before resuspension in 0.5 ml of the same buffer.…”

Lues maligna in an HIV-infected patient

“…The local immune response to T. pallidum may be critical to the development of clinical manifestations as well as to the clearance of spirochetes from infected tissues. However, relatively little is known about the local immune responses to T. pallidum in skin and other body sites, and virtually nothing is known about the subpopulations of immune cells in the lesions of patients with syphilis co-infected with HIV 11 .…”