Interleukin (IL)-2 and IL-12 responses to Chlamydia trachomatis infection in adolescents.

Chlamydia trachomatis infects epithelial cells at the mucosal surface. While in vitro and animal studies have shown changes in mucosal T(H)1-associated cytokines in the presence of C. trachomatis infection and with its progression to the upper genital tract or clearance, in vivo cytokine responses to chlamydial infection in humans are not well understood. Using a quantitative enzyme-linked immunosorbent assay (ELISA), we examined the endocervical production of two T(H)1-associated cytokines, i.e. interleukin (IL)-2 and IL-12, in relation to C. trachomatis infection in adolescents. At a randomly selected visit for 396 females, median endocervical IL-2 levels were significantly lower (190 versus 283 pg/ml, P = 0.02) and median IL-12 levels significantly higher (307 versus 132 pg/ml, P < 0.001) in subjects testing positive versus negative for C. trachomatis. These divergent T(H)1-associated cytokine responses were: (1) confirmed in paired analyses of 96 individuals before and after infection within 6-month intervals, (2) reversible in 97 patients who cleared infection during consecutive visits, (3) not attributable to sociodemographic factors or other genital infections and (4) independent of common genetic variants at the IL2 and IL12B loci associated previously with differential gene expression. From these findings we infer that increased IL-12 and decreased IL-2, observed commonly during mucosal inflammation, are important features of mucosal immune defence against C. trachomatis infection.

Induction of specific immune responses in the genital tract of women after oral or rectal immunization and rectal boosting with Salmonella typhi Ty 21a vaccine.

The purpose of this study was to determine the efficacy of intestinal tract immunization in the induction of specific antibodies in human female genital tract secretions. Live attenuated typhoid vaccine Ty 21a was administered to three groups of healthy female volunteers, who were not using hormonal contraceptives. Group 1 included 15 women vaccinated orally. Group 2 included seven of the same women, who were vaccinated rectally 6 months later. Group 3 included 11 volunteers, who were vaccinated rectally. Salmonella-specific antibodies of IgG and IgA were measured in vaginal lavage and cervical mucus after oral or rectal primary vaccination. Salmonella-specific antibodies measured 1 month after rectal booster vaccination demonstrated significant increases in vaginal fluids and cervical mucus and were dominated by IgA. These results indicate that specific antibodies in the human female genital tract induced by primary vaccination can be enhanced by subsequent rectal administration of vaccines.

Immunology and the REACH study: HIV immunology and preliminary findings. Reaching for Excellence in Adolescent Care and Health.

This review paper presents the immunology findings in human immunodeficiency virus (HIV) infected and uninfected youth in the Reaching for Excellence in Adolescent Care and Health (REACH) Project within the context of basic and HIV immunology concepts. Methods employed in the study for specimen collection, management, and laboratory analysis are presented. This paper reviews published analyses of cross-sectional data; longitudinal analyses are underway. These preliminary data extend the work of others in demonstrating the potential for substantial thymic reserve in youth. This finding in HIV infected adolescents has implications for a fuller response to antiretroviral or immune-based therapies compared to that seen in adults. Dysregulation in mucosal immunity may appear before systemic HIV effects are seen and requires attention particularly to screening and treatment of genital co-infections. REACH has demonstrated gender differences in immunologic measures irrespective of HIV infection status.

Douching practices among HIV infected and uninfected adolescents in the United States.

PURPOSE: To characterize sexual behaviors and sociodemographic factors that are associated with douching among geographically diverse adolescent women with and without HIV infection. METHODS: HIV infected subjects recruited preferentially and behaviorally comparable high-risk HIV uninfected subjects were enrolled in a prospective HIV study from 15 sites in 13 U.S. cities. Baseline interview data from 1996 to 1999 for females aged 12 to 19 years were analyzed using one-way analysis of variance and multiple logistic regression. RESULTS: Among the 342 females/young women, 74.9% were black (non-Hispanic), 11.1% Hispanic/Latina, and 14.0% white or other race/ethnicity; 63.5% were HIV infected. Young women who had dropped out of high school comprised 23.4% of subjects. In the 3 months before the interview, 179 (52.3%) adolescents had douched at least once. In a multivariable logistic regression model, recent douching was more common among sexually active females (OR = 2.2; 95% CI: 1.2-4.2), Blacks (OR = 2.2; 95% CI: 1.2-4.1 vs. Hispanics/Whites/others), females who dropped out of high school (OR = 2.1; 95% CI: 1.2-3.7), and HIV infected females (OR = 1.7; 95% CI: 1.04-2.7). CONCLUSIONS: In this nationwide study, adolescents who are sexually active, African-American, dropped out of high school, and HIV infected were most likely to douche. Interventions to discourage douching should pay special attention to these populations.

Serologic response to hepatitis B vaccine in HIV infected and high-risk HIV uninfected adolescents in the REACH cohort. Reaching for Excellence in Adolescent Care and Health.

PURPOSE: To evaluate hepatitis B (HBV) vaccine response rates in HIV infected and high-risk HIV uninfected youth and examine associations with responsiveness in the HIV infected group. METHODS: Cohorts within the Reaching for Excellence in Adolescent Care and Health (REACH) study population were defined based on receipt of HBV vaccine both retrospectively and prospectively. Sero-responsiveness was determined by HBsAb measurements. Testing was done for HBsAg, HBsAb, and HBcAb. For HBsAb, a value of > 10 International Units per liter was considered a positive response, and the data were collected as either positive or negative from each of the reporting laboratories. Covariates of responsiveness were explored in univariate and multivariate models for each cohort. RESULTS: Sixty-one subjects had received a three-dose vaccination course at the time of entry into REACH. HIV uninfected subjects had significantly higher rates of response by serology compared with HIV infected subjects (70% vs. 41.1%; chi(2) = .05; RR = .586, 95% CI: .36-.96). By the time of an annual visit 43 subjects had received three vaccinations with at least one occurring in the study period. The rates of response were similar for the HIV infected and uninfected groups (37.1% vs. 37.5%) in this cohort. Univariate and multivariate analysis in the prospective HIV infected group (N = 35) found an association between elevated CD8(+)/CD38(+)/HLA-DR(+) T cells and lack of HBV vaccine responsiveness (6.7% vs. 60%; chi(2) = .03; RR = .12, 95% CI: .02- .55). CONCLUSIONS: The poor HBV vaccine response rate in the HIV uninfected high-risk adolescents was unexpected and suggests that HBV vaccination doses have not been optimized for older adolescents. This is the first report of decreased responsiveness in HIV infected subjects being associated with elevated CD8(+)/CD38(+)/HLA(-)DR(+) T cells and suggests that ongoing viral replication and concomitant immune system activation decreases the ability of the immune system in HIV infected subjects to respond to vaccination.

Cytokine profile in genital tract secretions from female adolescents: impact of human immunodeficiency virus, human papillomavirus, and other sexually transmitted pathogens.

Quantitative enzyme-linked immunosorbent assays were used to measure interleukin (IL)-2, IL-10, and IL-12 in cervical secretions from female adolescents with and without sexually transmitted infections. Compared with human immunodeficiency virus [HIV]-negative patients, HIV-positive patients had higher concentrations of IL-10 (118.2 pg/mL vs. 34.5 pg/mL; P=.002) and IL-12 (175.5 pg/mL vs. 85.1; P=.03). IL-2 concentrations were not statistically different. Furthermore, genital tract infections were predictors of IL-10 and IL-12 concentrations. Coinfection with HIV and human papillomavirus predicted the highest IL-10 concentrations; coinfection with HIV, human papillomavirus, and other sexually transmitted pathogens predicted the highest IL-12 concentrations. The data indicate that concomitant infection of the genital tract with HIV and other viral, bacterial, or protozoan pathogens influences the local concentrations of some immunoregulatory cytokines.

Prevalence of and risks for cervical human papillomavirus infection and squamous intraepithelial lesions in adolescent girls: impact of infection with human immunodeficiency virus.

CONTEXT: Data suggest that in adults, human papillomavirus (HPV) infections and their sequalae, squamous intraepithelial lesions (SILs), occur more commonly among human immunodeficiency (HIV)-infected women because of the HIV-associated CD4+ T-cell immunosuppression. Since adolescents are more likely to be early in the course of HIV and HPV infections, the study of both infections in this age group may help elucidate their initial relationship. OBJECTIVE: To examine the prevalence of and risks for cervical HPV infection and SILs by HIV status in a population of adolescent girls. PARTICIPANTS: Subjects recruited at each of the 16 different US sites participating in a national study of HIV infection in adolescents. MAIN OUTCOME MEASURES: Cervical HPV DNA findings using polymerase chain reaction detection techniques and Papanicolaou smear from baseline visits. Infection with HPV was categorized into low- (rarely associated with cancer) and high- (commonly associated with cancers) risk types. RESULTS: Of 133 HIV-infected girls, 103 (77.4%) compared with 30 (54.5%) of 55 noninfected girls were positive for HPV (relative risk [RR], 1.4; 95% confidence interval [CI], 1.1-1.8). The risk was for high-risk (RR, 1.8; 95% CI, 1.2-2.7) but not low-risk (RR, 1.2; 95% Cl, 0.4-3.9) HPV types. Among the girls with HPV infection, 21 (70.0%) of the non-HIV-infected girls had normal cytologic findings compared with only 29 (29.9%) of the HIV-infected girls (P<.001). Multivariate analysis showed that HIV status was a significant risk for HPV infection (odds ratio [OR], 3.3; 95% CI, 1.6-6.7) and SIL (OR, 4.7; 95% CI, 1.8-14.8), but CD4 cell count and viral load were not associated with infection or squamous intraepithelial lesions. Only 9 girls had a CD4+ T-cell count of less than 0.2 cell X 10(9)/L. CONCLUSIONS: High prevalence of HPV infection in both groups underscores the risky sexual behavior in this adolescent cohort. Rates of HPV infection and SILs were higher among HIV-infected girls, despite similar sexual risk behaviors and the relatively healthy state of our HIV-infected group. Infection with HIV may enhance HPV proliferation through mechanisms other than CD4 immunosuppression, particularly early in the course of HIV infection.

HIV+ patients have increased lymphocyte infiltrates in CIN lesions.

OBJECTIVE: The objective of our study was to analyze immunocyte infiltrates in CIN lesions from HIV+ patients to assess whether local immunosuppression, defined as a decrease in T cell infiltrates, could explain the aggressive nature of CIN in HIV-infected patients. MATERIALS AND METHODS: Cervical tissue was obtained from 6 HIV+ CIN patients, 6 HIV- CIN patients, who underwent LLETZ (large loop excision of the transformation zone) for CIN, and 17 normal patients who underwent hysterectomy for benign indications. The following cell surface markers were analyzed: CD20 (B cells), CD4 (T helper cells), and CD8 (T suppressor/cytotoxic cells). Each tissue section was visualized with a Leica microscope at 400x and the image was captured for analysis by Harmony Group image analysis software. RESULTS: A significantly higher number of lymphocytes (both B and T cells) was detected in the stroma of HIV+/CIN tissue compared to either HIV-/CIN or normal tissue. There was also a significant increase in CD8+ cells in the HIV+/CIN group compared to HIV-/CIN or normal tissue. There was a trend toward a decreased CD4+/CD8+ ratio in the HIV+/CIN compared to the other two groups; however, this did not reach statistical significance. CONCLUSIONS: This study indicates that HIV+/CIN cervical tissue has a greater number of tissue lymphocytes recruited to the neoplastic site compared to HIV- individuals. In addition, HIV+ patients may have a decreased CD4/CD8 ratio in locally infiltrating immunocytes in CIN lesions. The local immunomodulatory effects of HIV may be detectable early in infection and therefore may explain the aggressive nature of CIN in the HIV+ patient.

Optimization of the weck-Cel collection method for quantitation of cytokines in mucosal secretions.

Measurement of immune components in mucosal secretions is important for the evaluation of local immunity at the mucosal surfaces. The Weck-Cel ophthalmic sponge provides a method for the collection of these secretions. The sponge absorbs a relatively large volume of material, therefore allowing for quantitation of multiple immune components. Additionally, it provides a method in which the same device may be used to collect specimens from different mucosal sites, such as the genital tract and oral cavity. This sampling technique has successfully been applied for collection and measurement of antibody in oral and genital tract secretions. The purpose of this work was to optimize the extraction of protein from the sponge matrix. Of particular interest was the recovery of cytokines from the sponge. Satisfactory recovery of the cytokines interleukin 1beta (IL-1beta), IL-2, IL-5, IL-12, IL-6, IL-8, IL-10, and granulocyte-macrophage colony-stimulating factor was obtained. However, IL-4 and gamma interferon recovery rates remained low. Using an alteration of the published extraction method, cytokine concentrations were measured in cervical secretions from women using oral contraceptives. The data revealed detectable concentrations of IL-6, IL-10, IL-8, and IL-12 on cycle days 9 and 20. The proposed technique provides an easy, practical, and consistent method for collection of nonconventional body fluids, such as cervicovaginal fluids and saliva, for the assay of immunoglobulins and several cytokines.

Cytokine and immunoglobulin concentrations in cervical secretions: reproducibility of the Weck-cel collection instrument and correlates of immune measures.

Elucidation of local immune response at the cervix is important for understanding and evaluating STD vaccine approaches currently being proposed. However, no well-validated method exists for the collection of cervical secretions for evaluation of cervical immune response. The purpose of this study was to determine the reproducibility of the Weck-cel sponge used to collect cervical secretions for immunological assessment. Additionally, it was possible to examine correlates of immunity as part of our investigation. Two cervical secretion specimens were collected sequentially from each of 120 women using Weck-cel sponges. Cervical secretions were collected prior to Pap smear sampling to avoid blood contamination. At the laboratory, the duplicate specimens were weighed and tested in replicate wells to determine the concentration of two cytokines (IL-10 and IL-12) and two immunoglobulin isotypes (IgG and IgA). IL-12, total IgG, and total IgA showed a strong correlation between samples from the same woman ranging from 0.78 to 0.84. Kappa coefficients obtained after categorizing assay results ranged from 0.62 to 0.67. Variance components analysis suggested that 69% to 85% of the variance observed was accounted for by between-women variance, with the remaining variability attributed to variation between samples collected from the same woman. IL-10 results were less reproducible than those obtained from the other assays examined, suggesting problems with the assay used to measure this cytokine rather than with the Weck-cel sampling instrument. Various factors were found to significantly correlate with cytokine and immunoglobulin measures at the cervix. Age and reproductive status were associated with all four immune measures; women over 50 years of age and those who were postmenopausal had increased concentrations of IL-10, IL-12, IgG, and IgA. Hemoglobin concentrations were positively correlated with IgG and IL-10 concentrations, but not with IgA or IL-12 concentrations, suggesting local production of IgA and IL-12. The concentration of all immune measures decreased with increasing volume of collection. No significant association was observed between time from collection to freezing of specimens and concentrations of cytokines or immunoglobulins. Overall, our data suggest that measurement of immunological parameters in cervical secretions collected using Weck-cel sponges are reproducible. In addition, various correlates of cytokine and immunoglobulin concentrations were identified.

Collection of cervical secretions does not adversely affect Pap smears taken immediately afterward.

Collection of cervical secretions for local immunological assessment requires that the secretions be collected prior to the Pap smear to avoid contamination with blood. The objective of the present study was to determine whether gentle collection of cervical secretions prior to a Pap smear collection influences the quality of the Pap smear. A total of 266 women were recruited. Half of the participants were assigned to collection of cervical secretions prior to Pap smear collection with Weck-cel sponges. The remaining half had only the Pap smear collection performed. Pap smear slides were reviewed and evaluated for quality by the Bethesda System adequacy criteria without knowledge of randomization. The proportions of limited or inadequate slides in the two study groups were compared by using the Pearson chi-square test. No significant differences were observed between the two study groups when overall Pap smear quality was evaluated (P = 0.29). Comparison of the two study groups with respect to individual adequacy criteria, including presence of air drying artifact, presence of obscuring blood, absence of metaplastic or endocervical cells from the transformation zone, scant cellularity, and presence of obscuring inflammatory cells, also revealed no significant differences between the two study groups. Results from the present study suggest that the collection of cervical secretions with Weck-cel sponges does not adversely impact the quality of subsequently obtained Pap smears.

Rectal immunization for induction of specific antibody in the genital tract of women.

The purpose of the current study was to examine potential routes of vaccine administration for the induction of antigen-specific responses in the genital tract of women. Sixteen women were enrolled in this study, and the level of influenza-specific antibodies induced in the genital tract was measured after rectal or intramuscular immunizations. Both methods of administration induced significant increases in the concentration of flu-specific IgA found in cervical secretions within 28 days after vaccination. Initially flu-specific IgG antibodies were not induced in the genital tract by either route. As expected both IgA and IgG flu-specific antibodies were dramatically increased in serum after intramuscular vaccination. In contrast, rectal administration did not induce significant IgA responses, and only small flu-specific IgG increases in serum. Six months after administration, IgA flu-specific antibody concentrations were significantly higher than baseline levels in vaginal secretions and saliva isolated from both subject groups and flu-specific IgG concentrations in cervical secretions were high in the rectal immunization group. The long-term presence of both IgG and IgA antibody in genital secretions suggests that rectal immunization may be an effective method for induction of immune protection in the genital tract of women.

Polyethylene glycol precipitates of serum contain a large proportion of uncomplexed immunoglobulins and C3.

High pressure liquid chromatography (HPLC) was used to fractionate redissolved polyethylene glycol (PEG) precipitates isolated from the sera of normal volunteers and from patients with IgA nephropathy (IgAN) and systemic lupus erythematosus (SLE), 2 diseases characterized by elevated levels of circulating immune complexes. The individual fractions were analyzed by solid phase ELISA for IgA, IgM, C3, IgG, and complexes of IgG-IgA and IgG-C3. Although PEG precipitates were enriched for high molecular weight IgA and IgG (presumably bound within CIC), significant amounts of IgM, unbound IgG and C3 were also present. The quantities of the PEG-precipitable proteins did not correlate with their serum concentrations. IgG-IgA and IgG-C3 complexes were found in all precipitates examined, but the levels of complexes were higher in both patient groups. These results indicate that PEG precipitates a considerable quantity of proteins not bound in immune complexes. There appeared to be greater protein precipitation from sera of the patient groups compared to the amount precipitated from the normal sera. These results suggest that an understanding of the mechanism of PEG precipitation may be important in defining abnormalities in IgAN, SLE and perhaps other diseases characterized by elevated levels of CIC. In addition, the possibility of undetected CIC in PEG precipitable material must be considered.

Alterations in expression and function of signal-transducing proteins in tumor-associated T and natural killer cells in patients with ovarian carcinoma.

Tumor-associated lymphocytes (TALs) freshly isolated from patients with cancer usually manifest reduced proliferative and cytolytic functions. To determine whether alterations in signal transduction contribute to functional impairments seen in TALs, we purified populations of T and natural killer (NK) cells by negative selection from ascites of seven patients with ovarian carcinoma. The average purity was 84 +/- 5% for CD3(+) TALs and 77 +/- 10% for CD3(-)CD56(+)CD16(+) TALs. Expression of several signal transduction molecules, including the CD3-epsilon, CD3-zeta, and FcepsilonRI-gamma chains, p56(lck) protein tyrosine kinase, and phospholipase C-gamma1, was studied in these cells using Western blotting. A marked decrease in expression of zeta and FcepsilonRI-gamma associated with CD3 or FcgammaRIIIA was observed in T or NK cells obtained from TALs, as compared to T or NK cells purified from normal peripheral blood. Expression of CD3-epsilon, as assessed using flow cytometry, Western blotting, or ELISA was also reduced in purified TAL-T cells relative to that in normal peripheral blood T cells. Surface expression of CD3 on T cells and FcgammaRIIIA on NK cells obtained from TALs was significantly decreased in comparison to normal peripheral blood lymphocytes (PBLs): the mean fluorescence intensity of CD3 was 277 +/- 18 for TAL-T (n = 7) versus 349 +/- 13 for PBL-T (n = 9) and that of CD16 was 58 +/- 1 for TAL-NK (n = 7) versus 385 +/- 55 for PBL-NK (n = 23) cells. These observations suggest a defect in assembly of T cell receptor and FcgammaRIIIA multicomponent transmembrane receptors, which are zeta and gamma dependent. In addition to alterations in expression, the function of these receptors was also modified, since cross-linking of CD3 on TAL-T and CD16 on TAL-NK cells with the respective monoclonal antibodies resulted in a pattern of protein phosphorylation that was distinct from that observed in normal PBLs. Expression of tyrosine kinase p56(lck) and its kinase activity were also depressed, while expression of phospholipase C-gamma1 appeared to be normal in most preparations of the TALs tested. In vitro proliferation of TAL-T in response to anti-CD3 monoclonal antibody and TAL-NK cells to interleukin 2 were significantly depressed as was the ability to produce IFN-gamma. In contrast, TAL-T cells were able to produce interleukin 10 at levels similar to those secreted by normal PBLs. Thus, in TALs obtained from patients with advanced ovarian cancer, alterations in expression and activity of signaling molecules were associated with reduced cellular functions such as proliferation and production of certain cytokines.

Normal uterine cervix: characterization of isolated lymphocyte phenotypes and immunoglobulin secretion.

PROBLEM: Isolation of viable cervical lymphocyte populations and characterization of their function in healthy tissue is necessary to understand immunity in the genital tract. METHODS: Normal, cervical tissue was digested using a multi-enzymatic digestion procedure. Lymphocytes were characterized using FACS analysis and ELISPOT analysis for immunoglobulin secreting cells. RESULTS: Following the digestion procedure, 0.16 x 10(6) +/- 0.8 cells/g of tissue with a viability of 90-98% were isolated from normal cervical tissue. FACS analysis determined that B lymphocytes were the predominant cell type in normal cervical tissue representing a significantly higher percentage than that found in peripheral blood (P = 0.015). T lymphocytes and NK cells represented a significantly lower percentage than that found in peripheral blood (P = 0.0001 and 0.026, respectively). The largest percentage of immunoglobulin secreting cells isolated were secreting IgG followed by IgA. A limited number of IgM secreting cells were detected. IgA2 secreting cells represented 34.46 +/- 4.6% of the total number of IgA plasma cells. CONCLUSION: These studies represent the first analysis of viable mononuclear cells isolated from normal cervical tissue. The results form a baseline from which it will now be possible to compare changes that occur at the cervical squamocolumnar junction in response to infection or neoplasia.

CD8+ T lymphocytes are recruited to neoplastic cervix.

ToliicIV distinguish normal cervical lymphocyte populations from phenotypes recruited to the cervix in response to cervical neoplasia, lymphocytes were isolated from normal and neoplastic cervix. A portion of the cervical transformation zone was obtained from 19 patients with pathologically confirmed cervical intraepithelial neoplasia and from 20 patients with normal cervices undergoing hysterectomy for benign indications. Mononuclear cells were harvested from cervical tissue using a serial, multienzymatic digestion procedure and enriched by density gradient centrifugation. Isolated cell populations were stained with surface marker-specific monoclonal antibodies and analyzed by fluorescent activated cell sorter to determine the percentage of B cells, total T cells, CD4+ T cells, CD8+ T cells, and natural killer (NK) cells. The distribution of circulating peripheral blood lymphocyte phenotypes was similar for both patients with neoplasia and normal controls. A marked disparity in the proportions of NK cells and T cells was demonstrated among lymphocyte phenotypes infiltrating the cervix. The percentage of CD4+ T cells and NK cells was significantly depressed (P = 0.04, P = 0.03, respectively) in dysplastic tissue as compared to normal cervical tissue. In contrast, the proportion of CD8+ T cells was significantly increased in the dysplastic tissue (P = 0.0001). Analysis of immunocompetent cells in the circulation appears to have little correlation with immunocytes present in the dysplastic epithelium. The depression in the proportion of CD4+ T lymphocytes and NK cells at the cervical squamocolumnar junction reflects a local recruitment of CD8+ T cells to the site of neoplasia in the cervix.

Immunological studies of IgA nephropathy in blacks reveal elevations of serum IgA2 as well as IgA1.

Although IgA nephropathy (IgAN) is recognized worldwide as the most common primary glomerulonephritis, the prevalence of this disease among American blacks is strikingly low despite the frequency of other renal disorders. We have previously described the clinical features of 27 black patients enrolled in a multicentre IgAN database; in this paper we report several immunological parameters of the disease in this population. Quantification of serum immunoglobulins revealed significantly higher concentrations of total IgA, IgA1 and IgA2 (P = 0.0001, 0.002 and 0.005 respectively) in the patients, but no significant increases in IgG or IgM. Examination of immunoglobulin synthesis by peripheral blood lymphocytes indicated relatively few differences in the secretion of immunoglobulins by patients compared to healthy American blacks. The spontaneous production of total IgA, IgA1, and IgA2 in patients was depressed compared to the control subjects (P = 0.02, 0.04, 0.03,), yet the ratio of IgA1:IgA2 was normal. Stimulation with pokeweed mitogen enhanced secretion of immunoglobulin in both subject groups. However, a significantly greater IgA1:IgA2 ratio was noted in the patients (P = 0.002). Circulating immune complexes containing C3 and IgA as well as C3 and IgM were elevated in the patients (P = 0.0006, 0.0003 and 0.02, respectively). These immunological aberrancies did not correlate with clinical manifestations of disease. These data suggest the immune abnormalities of black IgAN patients are similar to, but not identical with, those of white patients.

Shared idiotypes in mesangial deposits in IgA nephropathy are not disease-specific.

The antigenic specificity of the mesangial IgA in IgA nephropathy (IgAN) remains unknown. Because shared antigenic specificities may be reflected in the usage of shared idiotypes, we prepared five monoclonal anti-idiotypic antibodies (MoAbs) specific for the mesangial IgA eluted from the kidney of an IgAN patient. All five MoAbs reacted with the same idiotype, which proved to be of a public nature. Although the idiotype could be identified in the mesangial deposits of the majority of IgAN patients studied, it was not specific for the disease because it was also found in the glomerular deposits of other types of glomerulonephritis. The idiotype was also expressed in polyethylene glycol precipitates of sera and in pokeweed mitogen-induced plasma cells from both IgAN patients and healthy controls. The conclusion that no disease-specific idiotypes are present in the renal eluate was further supported by the failure to produce polyclonal anti-idiotypic antibodies by immunizing a rabbit with the eluted mesangial IgA. Our results support the concept that mesangial IgA deposits in IgAN are of a polyclonal nature.