Altered distribution of mannose-binding lectin alleles at exon I codon 54 in women with vulvar vestibulitis syndrome.

OBJECTIVES: Mannose-binding lectin (MBL) is active in the innate immune defense against microorganisms. In this study, we determined whether vulvar vestibulitis syndrome, a disorder of unknown etiology, was associated with an altered distribution of MBL alleles. STUDY DESIGN: Buccal swabs were obtained from women with vulvar vestibulitis syndrome in New York (62) and from 2 cities in Sweden (60), as well as control women in New York (48) and Sweden (51). DNA was tested for a single nucleotide polymorphism at codon 54 in exon I by polymerase chain reaction, endonuclease digestion, and gel electrophoresis. Blood samples were also obtained from the New York women and tested by ELISA for plasma MBL concentrations. The relationships between genotype, allele frequencies, blood MBL levels, and diagnosis were analyzed by Fisher exact test and one-way analysis of variance. RESULTS: The variant MBL allele, MBL*B, was detected in 35.5% and 26.7% of vulvar vestibulitis patients from New York and Sweden, respectively. Only 12.5% of New York controls (P=.007) and 9.8% of Swedish controls (P=.01) were MBL*2-positive. All women, with one exception, who were positive for MBL*B were MBL*A/MBL*B heterozygotes. Women who carried MBL*B had almost a 10-fold reduction in median plasma MBL concentrations (278 ng/mL), as opposed to women who were MBL*A homozygotes (1980 ng/mL) (P < .0001). CONCLUSION: MBL*B carriage and reduced plasma MBL levels are more common in women with vulvar vestibulitis syndrome than in control patients, and may contribute to symptomatology in a subset of patients.

Differential characterization of women with vulvar vestibulitis syndrome.

OBJECTIVE: We differentiated women with vulvar vestibulitis syndrome into subgroups on the basis of the time of symptom onset, a history of recurrent vulvovaginal candidiasis, and the interleukin-1 receptor antagonist gene polymorphism. STUDY DESIGN: One hundred sixty-two consecutive patients with strictly defined vulvar vestibulitis syndrome were asked to fill out a questionnaire with the assistance of their gynecologist. A buccal sample was collected from each subject for the analysis of interleukin-1 receptor antagonist gene polymorphism; vaginal and vestibular microbial investigations were performed. RESULTS: Symptoms began with the first act of coitus in 20.4% of patients. A history of a recurrent Candida vulvovaginal infection was reported in 42.6% of patients; 25.9% of the patients were positive for the homozygous interleukin-1 receptor antagonist 2,2 genotype. Women with primary vulvar vestibulitis syndrome differed from women with secondary vulvar vestibulitis syndrome; women with primary vulvar vestibulitis syndrome were younger at the time of the onset of the symptoms (23.8 vs 31.2 years, P <.0001) and had never been pregnant (84.8% vs 61.2%, P <.0001). Women with a history of recurrent Candida vulvovaginitis differed from the other subjects by having a higher frequency of constant vestibular pain (40.6% vs 20.4%, P =.005), a vaginal discharge (79.7% vs 45.2%, P <.0001), and dysuria (62.3% vs 29.0%, P =.0001). Women who were homozygous for interleukin-1 receptor antagonist 2,2 genotype had an earlier onset of symptoms (26 years) than did women who were allele 1 homozygotes (31.3 years, P <.05). They also had a shorter duration of symptoms (4.1 vs 5.9 years, P <.05) and a higher frequency of allergy (47.6% vs 23.4%, P =.002). Human papillomavirus in the vaginal vestibule occurred at a greater frequency in women who were homozygous for interleukin-1 receptor antagonist 2,2 genotype. CONCLUSION: Subgroups of women with vulvar vestibulitis syndrome may be differentiated by symptomatic and genetic variables.

Telomerase activity in HPV-associated vulvar vestibulitis.

OBJECTIVE: To find a possible correlation between telomerase activity, mean telomere length and human papillomavirus (HPV) presence and type in vulvar vestibulitis. STUDY DESIGN: Twenty-two tissues excised during surgery for the treatment of severe vulvar vestibulitis and nine control tissue samples were tested for telomerase activity, mean telomere length, and HPV presence and type. RESULTS: Thirty-six percent of the tissues from vestibulitis patients were infected with HPV, mainly type 16/18, and none of the control tissue samples showed presence of HPV DNA (P < .02). Telomerase activity was detected in all tissues harboring HPV DNA, whereas only 64% of tissues without HPV DNA exhibited telomerase activity (P < .02). The mean telomere length was unchanged as compared to control samples. CONCLUSION: Telomerase activity in vestibulitis may be increased as a result of HPV infection, suggesting that HPV infection may play a role in the etiology of some cases of vulvar vestibulitis.

Interleukin 1 receptor antagonist gene polymorphism in women with vulvar vestibulitis.

OBJECTIVE: Vulvar vestibulitis is a chronic inflammatory syndrome of unknown cause and pathogenesis. We examined the relation between vulvar vestibulitis and polymorphisms in the gene coding for the interleukin 1 receptor antagonist, a naturally occurring down-regulator of proinflammatory immune responses. STUDY DESIGN: Cells from the lower genital tract of 68 women with vulvar vestibulitis, 343 women with no history of vulvodynia, and 40 women with human papillomavirus cervical infection were tested by polymerase chain reaction for the different alleles of the gene encoding for interleukin 1 receptor antagonist. The presence of human papillomavirus in the specimens was determined by polymerase chain reaction with the use of degenerate consensus primers to the conserved L1 gene. RESULTS: Allele 2 of the gene encoding the interleukin 1 receptor antagonist was present in homozygous form in 52.9% of women with vulvar vestibulitis. In marked contrast only 8. 5% of the control women and 2.5% of women with human papillomavirus were homozygous for this allele (P

Pathogenesis of HSV-1/2 induced vaginitis/vulvitis of the mouse: dependence of lesions on genetic properties of the virus and analysis of pathohistology.

A scoring system for herpes simplex virus (HSV) induced vaginitis/vulvitis in Balb/c mice was delineated from vaginal infections. Four degrees of vaginitis/vulvitis could be distinguished after infection with suitable strains of HSV despite nearly identical replication rates. The time course of replication, inflammation and pathohistology was compared further. Grade 0 was defined by lack of symptoms despite presence of strong replication, which was detectable at days 3-6. Focal necrotic lesions of the epithelial layer were present containing HSV-specific antigens. DNA could be detected by hybridization only in the outer zone of these areas. At day 6 these zones began to be re-epithelialized. In the vaginal lumen abundant detached epithelial cells and granulocytes were already present by day 2. Grade 1 was macroscopically characterized by a slight inflammation commencing on days 5-6. Replication and antigens in the epithelium were found on days 2-6. HSV-antigens were only detected above the basal membrane, and some infiltration with granulocytes and lymphocytes was observed below the basal membrane at day 4. Grade 2 showed strong redness and inflammation as well as hyperemia. Cellular infiltrates were present in the large antigen containing epithelial lesions and below the basal membrane. From day 4 on, neurons were HSV-antigen and DNA positive and macrophages in the stroma contained antigen. The vulva was also shown to be involved. Grade 3 exhibited prolonged severe hyperemia, and destruction of the epithelium and the stroma with necrosis and infiltration, especially of the vulva. This grading system was shown to depend on certain unknown genetic properties of HSV-strains. Neither thymidine-kinase activity, replication in macrophages, fusion activity of strains nor presence or absence of the Hpa I P-fragment were shown to be of importance for severity of vaginitis/vulvitis. Vaginitis/vulvitis was shown to be an all or none response to HSV independent of the rate of replication. The set of virus genes responsible for neuroinvasiveness after vaginal or i.p. inoculation was found to be different. The time course of replication (mainly days 3-6) and inflammation (days 5-10) indicates that inflammation seems to be a secondary immunological phenomenon induced later by the replication phase of HSV. Our system could be useful for separately testing drugs with antiviral and anti-inflammatory properties.