Mesh induced fibrosis: The protective role of T regulatory cells.

Polypropylene mesh is widely used in urogynecologic surgery, but complications rates (pain and exposure) approach 10%. Emerging evidence implicates the adaptive immune system in regulating the foreign body response to mesh, particularly regulatory T cells (Tregs), which modify macrophage differentiation and down-regulate CD8+ effector T cells. We hypothesize that Tregs protect against a profibrotic response, a likely mechanism of pain complications. Here, thin sections of mesh-tissue complexes removed for the primary complaint of pain (N = 14) or exposure (N = 15) were labeled for CD8, CD4 (Th), and FoxP3 (Tregs) via immunofluorescence. The same sections were analyzed for localized collagen deposition via a customized semi-quantitative assessment (0.25 mm2 grid) after trichrome staining. TGF-ß1 concentrations were determined by enzyme-linked immunosorbent assay. Fewer Treg and CD4+ cells were found in fibrotic areas versus non-fibrotic areas (503 and 550/cm2 fewer, respectively, both P < 0.001). TGF-ß1 was higher in mesh samples compared to autologous control biopsies. TGF-ß 1 inversely correlated with age, r -0.636(p = 0.008). No differences were found in T cell subgroups or fibrotic indices between pain and exposure groups. A moderate inverse relationship was found between TGF-ß1 and Tregs (r -0.402, P = 0.009). Tregs were present up to 12 years after mesh implantation, challenging the assumption that the adaptive immune response to a foreign body is transient. In conclusion, the inverse relationship between fibrosis and Tregs, and TGF-ß1 and Tregs points to a protective role of these cells. Similar immunologic responses in patients with pain and exposure suggest these complications exist along a spectrum. STATEMENT OF SIGNIFICANCE: The use of polypropylene mesh has been associated with improved outcomes in urogynecologic surgery, but is associated with significant complications, including pain and exposure through the vaginal epithelium. The host immune response features a prolonged inflammatory reaction containing innate immune cells and T lymphocytes clustered in capsules around the mesh fibers. This study uncovers the inverse relationship between T regulatory cells and the extent of fibrosis around the mesh, suggesting an anti-fibrotic effect. In addition, concentrations of T regulatory and T effector cells and levels of fibrosis connect these two most common complications into one mechanistic pathway. These new insights into the immune response to implanted mesh are an important step in understanding the causes of these surgical complications.

Erosions on a prolapsed uterine in an old woman: an unusual manifestation of pemphigus vulgaris.

Vaginal involvement in pemphigus vulgaris has previously been described. In all those cases a pelvic examination was needed to explore the lesions. We describe a patient with pemphigus vulgaris who had pemphigus erosions on a prolapsed uterus (i.e., on the everted surface of vagina). The patient had widespread lesions of pemphigus in other mucosal and cutaneous sites. Biopsy, antibodies against desmoglein 1 and 3, and direct and indirect immunofluorescence were confirming. The erosions on the prolapsed uterus were resistant to treatment; other mucosal and cutaneous lesions responded rapidly to prednisolone and azathioprine. After lowering the dose of prednisolone the patient was referred to a gynecologist for a vaginal hysterectomy. This case was unique because her vaginal lesions could be easily examined and followed.

A histological and immunohistochemical study of neuropeptide containing somatic nerves in the levator ani muscle of women with genitourinary prolapse.

BACKGROUND: To evaluate the changes occurring in the somatic innervation throughout the levator ani muscle in women with genitourinary prolapse and stress urinary incontinence (SUI). METHODS: Thirty-four patients with genital prolapse entered the study and ten subjects with non-malignant pathologies acted as a control group. All patients were evaluated by urodynamic investigation and an electromyographic study of pelvic floor muscles to define the type of urinary incontinence. Biopsy samples were obtained from both groups of patients: the site of muscle biopsies were left and right part of perirectal pubococcygeus muscle. The evaluation of immunoreactivity was semiquantitative and based on staining intensity and distribution. RESULTS: In all cases, S-100 protein and NSE immunoreactivities were found in nerve fascicles running throughout the striated muscle. NPY and VIP positivities were more intense and diffuse, whereas SP immunoreactivity was quite scanty. The different patterns of NPY and VIP expression changed in relation to degree of genital prolapse and to the presence of SUI. CONCLUSIONS: Our immunohistochemical study shows the presence in the pelvic floor of neurons that are able to synthesize neuropeptides. The lower immunoreactivity score of same neuropeptides (VIP, NPY) observed among patients with third degree genital prolapse and with SUI could be related to biochemical damage of the neurons with subsequent lower production of chemical messengers.

Antibodies to Herpes simplex virus in Jewish women with cervical cancer and in healthy Jewish women of Israel.

Herpes simplex virus (HSV) antibody titers were examined in sera from 39 Jewish women with squamous cell carcinoma of the uterine cervix (CaCx) and in sera from controls matched by age and country of origin. Highly significant differences were found between the cases and controls for both HSV type 1 (HSV-1) and HSV type 2 (HSV-2). Compared to findings in other demographic areas, the geometric mean titer (GMT) of HSV-1 among the CaCx cases were considerably higher, whereas the GMT for HSV-2 was in the same range. The percentage of HSV-2-positive patients, as defined by the HSV-2/HSV-1 antibody titer ratio was low compared to that found in other demographic areas; this was presumably due to the high incidence of HSV-1 infection in the population. The HSV-1 and HSV-2 infection rate in the Israeli Jewish female population was estimated by antibody titers for 94 healthy subjects. The GMT of HSV-1 was considerably higher, whereas the GMT of HSV-2 was lower, than those reported elsewhere. The association found previously between HSV-2 and CaCx remained true for Jewish women. Their low incidence of CaCx, which did not seem to result from lower susceptibility, might be explained by the low incidence of HSV-2 infection.