IVIg therapy increases delivery birthweight in babies born to women with elevated preconception proportion of peripheral blood (CD56+/CD3-) natural killer cells.

In this study, the authors investigated: (1) whether elevated preconception peripheral blood proportion of CD56+/CD3- lymphocytes (NK cells) was associated with low delivery birthweight in high risk women, and (2) whether intravenous immunoglobulin (IVIg) therapy could be used to improve the delivery outcome in these women. MATERIALS AND METHODS: Sixty-six women who had singleton deliveries were divided into four groups. Group 1: 16 women with elevated preconception NK cells (>12%) using IVIg, group 2: eight women with similar elevated preconception NK cells not using IVIg, group 3: 32 women with non-elevated preconception NK cells (≤12%) using IVIg, and group IV: ten women with similar non-elevated preconception NK cells not using IVIg. These groups were similar with regards to patient age, test results, and history. RESULTS: Mean gestational age (±cmaz, GSD) of babies at delivery wa± 39.3 ± 1.7± 37.4 ± 3.7± 38.5 ± 1.3, an± 38.7 ± 1.5 weeks, for groups 1, 2, 3 and 4, respectively. Mean birthweight of babies at delivery was± 3,267 373,±2,654 ± 627,±3,129 ± 527, and±3,202 ± 357 grams, respectively. Birthweight was significantly higher for1group I vs. group 2 (p = 0.006) but not for groups 1 vs. group 3. There was no significant difference between the groups for preeclampsia rate, C-section rate or preterm delivery rate. CONCLUSION: In women with elevated preconception peripheral NK cells, mean birthweight at delivery is low without IVIg therapy ±2,654 ± 627 grams) but significantly improved with IVIg therapy ±3,267 ± 373 grams). In high risk wom without preconception NK cell elevation, mean birthweight at delivery is not further-increased with IVIg therapy ±3,202 ± 357 grams with IVIg vs.±3,129 ± 527 grams without IVIg). IVIg may be a treatment option for women with preconception NK elevation at risk of a low birthweight baby. Preconception immune testing may be a tool for determining which patients will benefit from IVIg therapy. Larger repeat studies are needed for confirmation.

Decreased CD57 lymphocyte subset in patients with chronic Lyme disease.

BACKGROUND: Chronic Lyme disease (LD) is a debilitating illness caused by tickborne infection with the spirochete Borrelia burgdorferi. Although immunologic abnormalities appear to play a role in this disease, specific immunologic markers of chronic LD have not been identified. METHODS: We evaluated 73 patients with chronic LD for lymphocyte subset abnormalities using flow cytometry. Of these, 53 patients had predominant musculoskeletal symptoms, while 20 patients had predominant neurologic symptoms. The estimated duration of infection ranged from 3 months to 15 years, and all patients had positive serologic tests for B. burgdorferi. Ten patients with acute LD (infection less than 1 month) and 22 patients with acquired immunodeficiency syndrome (AIDS) served as disease controls. RESULTS: All 31 chronic LD patients who were tested prior to antibiotic treatment had significantly decreased CD57 lymphocyte counts (mean, 30+/-16 cells per microl; normal, 60-360 cells per microl, P<0.001). Nineteen of 37 patients (51%) who were tested after initiating antibiotic therapy had decreased CD57 levels (mean, 66+/-39 cells per microl), and all five patients tested after completing antibiotic treatment had normal CD57 counts (mean, 173+/-98 cells per microl). In contrast, all 10 patients with acute LD and 82% of AIDS patients had normal CD57 levels, and the difference between these groups and the pre-treatment patients with chronic LD was significant (P<0.001). Patients with chronic LD and predominant neurologic symptoms had significantly lower mean CD57 levels than patients with predominant musculoskeletal symptoms (30+/-21 vs. 58+/-37 cells per microl, P=0.002). CD57 levels increased in chronic LD patients whose symptoms improved, while patients with refractory disease had persistently low CD57 counts. CONCLUSIONS: A decrease in the CD57 lymphocyte subset may be an important marker of chronic LD. Changes in the CD57 subset may be useful to monitor the response to therapy in this disease.

Treatment of severe atopic dermatitis by topical immune modulation using dinitrochlorobenzene.

We present the results of a small uncontrolled pilot trial which suggest that contact sensitization to dinitrochlorobenzene and repeated weekly applications significantly improve the clinical status of severe atopic dermatitis in adults. Although no changes were noted in circulating levels of either lymphocyte subset populations or the serum cytokines assayed in this trial, our observations may be due to topical immune modulation by dinitrochlorobenzene. Larger controlled studies of dinitrochlorobenzene treatment in atopic dermatitis are warranted.

Successful treatment of immunologic abortion with low-dose intravenous immunoglobulin.

OBJECTIVE: To evaluate the efficacy of low-dose intravenous immunoglobulin (IVIG) treatment in older women with immunologic abnormalities and recurrent spontaneous abortion (RSA), a condition referred to as immunologic abortion. DESIGN: Prospective clinical trial. SETTING: Outpatient referral practice. PATIENT(S): Forty-seven women were enrolled in the study. The mean age of the women was 37 years (range, 28-45 years), and the mean number of prior miscarriages was 3.7. Immunologic abnormalities included antiphospholipid antibodies (32%), antithyroid antibodies (53%), antinuclear antibodies (28%), antiovarian antibodies (2%), increased natural killer cells (40%), increased immunoglobulin (Ig)M level (28%), and increased CD4/CD8 T-cell ratio (15%). One patient had IgA deficiency, and three women had endometriosis. Thirty-one of the 47 patients (66%) had more than one immunologic abnormality. INTERVENTION(S): Treatment with IVIG at a dose of 0.2 g/kg within 2 weeks of attempted conception. Once conception was achieved, IVIG treatment was continued on a monthly basis at the same dose through 26-30 weeks of gestation. MAIN OUTCOME MEASURE(S): Successful pregnancy or recurrent abortion. RESULT(S): Of the 47 women, 36 received initial IVIG treatment, and 24 subsequently became pregnant. Of these women, 20 continued IVIG treatment through 26-30 weeks of gestation, and 19 (95%) had a successful term pregnancy. Four women discontinued IVIG therapy after 10-12 weeks of gestation, and 3 (75%) had a successful pregnancy outcome. Of the 11 women who refused IVIG therapy, 7 became pregnant, and all 7 miscarried. The difference in pregnancy success rate between the IVIG-treated and untreated groups was significant (P=.001). Three women had adverse reactions during the low-dose IVIG infusion, and these reactions resolved when the IVIG brand was changed. Fetal abnormalities were not observed. CONCLUSION(S): Low-dose IVIG therapy is beneficial for older women with immunologic abortion. The optimum duration of IVIG treatment in these women requires further study.

Serum silicon levels are elevated in women with silicone gel implants.

The metabolic fate of silicone gel leaked into the body from an implant is unknown. In this study, serum from 72 women with silicone gel breast implants and 55 control women was blindly assayed by inductively coupled plasma atomic emission spectroscopy (ICP-AES) for elemental silicon. Samples were processed using materials free of silicon. The mean silicon level in controls was 0.13 +/- 0.07 mg/l (range 0.06-0.35 mg/l), while in implant patients, the mean was significantly higher at 0.28 +/- 0.22 mg/l (range 0.06-0.87 mg/l) (P < 0.01, Student's t-test with correction for unequal variances). Using the mean of the control group + 2 SD as a cutoff for normal range (0.27 mg/l), 25/72 (34.7%) implant patients exceeded this value, compared with 2/55 (3.6%) controls. There was no significant correlation between past rupture of one or both implants, current rupture at the time of the blood draw or the number of years with implants and silicon levels. The results suggest that elevations of serum silicon are seen in many women with silicone gel breast implants. The kinetics of this elevation and the actual chemical species of the measured silicon remain to be determined.

Elevated serum silicon levels in women with silicone gel breast implants.

The metabolic fate of silicone gel leaked from an intact or ruptured prosthesis is unknown. In this study, serum was blindly assayed by inductively coupled plasma atomic emission spectroscopy (ICP-AES) for elemental silicon in 72 women with silicone gel breast implants and 55 control women (mean age 48 yr, both groups). Blood was drawn and processed using silicon-free materials. The mean silicon level in controls was 0.13 +/- 0.07 mg/L (range 0.06-0.35 mg/L), whereas in implant patients, the mean was significantly higher at 0.28 +/- 0.22 mg/L (range 0.06-0.87 mg/L) (P < 0.01, Student's t-test with correction for unequal variances). Using the mean of the control group + 2 SD as a cutoff for normal range (0.27 mg/L), 25/72 (34.7%) implant patients exceeded this value, compared with 2/55 (3.6%) controls. There was no significant correlation between past rupture of one or both implants, current rupture at the time of the blood draw, or the number of years with implants and silicon levels. The results suggest that serum silicon levels are elevated in many women with silicone gel breast implants. The chemical species involved and kinetics of this elevation remain to be determined.

Clinical and immunologic evaluation of HIV-infected patients treated with dinitrochlorobenzene.

BACKGROUND: Promotion of cell-mediated immunity appears to be an important goal in the control of HIV infection. Topical dinitrochlorobenzene (DNCB) stimulates systemic cell-mediated immunity via the induction of cutaneous delayed-type hypersensitivity. OBJECTIVE: Our goal was to evaluate the clinical and immunologic effects of chronic DNCB application in a group of 24 HIV-infected patients. METHODS: We observed the patients for a mean of 28 months (range, 14 to 44 months). Of the 24 patients, 13 continued weekly DNCB application throughout the study (the compliant group), and 11 discontinued DNCB use after a mean of 10.9 months (the noncompliant group). RESULTS: Two of the 13 compliant patients progressed to AIDS; none of these patients died. In contrast, AIDS developed in 5 of the 11 noncompliant patients and four of these patients died. Analysis of lymphocyte subsets revealed significant increases in natural killer cells and activated/cytotoxic CD8 T-cell subsets in the compliant group. In contrast, these cellular immune-related lymphocyte subsets decreased in the noncompliant subjects. Although CD4 T-cell levels decreased in both groups, there was a significantly greater drop in the noncompliant patients. CD8+CD38+ T cells increased significantly in both groups. CONCLUSION: Chronic DNCB application appears to have a beneficial clinical and immunomodulatory effect in HIV-infected patients.

An improved method for monitoring efficacy of anti-retroviral therapy in HIV-infected individuals: a highly sensitive HIV p24 antigen assay.

Circulating human immunodeficiency virus (HIV) p24 antigen levels were measured by a highly sensitive HIV p24 antigen-capture enzyme-linked immunosorbent assay (ELISA) in patients with acquired immunodeficiency syndrome (AIDS) and AIDS-related complex (ARC) otherwise negative for HIV p24 antigen measured by a commercial antigen-capture ELISA. The assays were performed at baseline and at several intervals during treatment with either zidovudine (ZDV) or dideoxyinosine (ddl). To further enhance the rate of antigen detection, serum was pretreated with hydrochloric acid to denature antibody in immune complexes. Utilizing this assay system, we monitored these patients for drug efficacy. HIV p24 antigen levels obtained by using this sensitive assay decreased in 3 of 8 patients receiving ZDV during 8 weeks of ZDV treatment. Similarly, ddl administration was associated with a decrease of HIV p24 antigen levels in 3 of 5 patients. Thus, the use of the highly sensitive HIV p24 antigen assay permitted the monitoring of surrogate HIV p24 antigen as a measure of efficacy of anti-retroviral therapy in all of these patients who were otherwise HIV p24 antigen-negative at the onset of anti-retroviral therapy.

Immune activation markers and AIDS prognosis.

Four assays for serum levels of cellular products of immune activation were examined as prognostic markers for AIDS in a prospective study of asymptomatic HIV-seropositive homosexual men. Baseline serum values of beta 2-microglobulin (beta 2M), neopterin, soluble CD8 (sCD8), and soluble interleukin-2 receptor (sIL-2R) for 185 men were examined univariately and multivariately as predictors of AIDS during 36 months of follow-up. Thirty-three cases of AIDS (18%) were diagnosed during the follow-up period. All four assays correlated highly with each other (r = 0.48-0.63), and all four were good univariate predictors of AIDS and comparable to CD4 lymphocyte count. beta 2M, neopterin, and sCD8 predicted AIDS independently of both CD4 count and HIV p24 antigen or p24 antibody in multivariate analysis. Within the range of CD4 count 200-499 x 10(6) cells/l, an immune activation marker used in combination with an assay for p24 antigen identifies those at 3-6% risk of AIDS over 36 months (low risk on both assays) and those at 63-86% risk (high risk on both assays). These results can be used to guide physicians and patients making decisions about treating asymptomatic HIV infection with zidovudine in individuals with CD4 lymphocyte count of 200-499 x 10(6) cells/l.

Chronic mastopathy and breast cancer. A follow-up study.

Over an average period of seven years 2,9000 cases of benign breast lesions diagnosed by biopsy between 1948 and 1973 in the Department of Pathology, Kaiser Foundation Hospital, Oakland, were followed for breast cancer development. When classified according to traditional diagnostic categories, the cancer incidence per 1,000 person-years varies between 2.7 and 7.9 and appears to be elevated in comparison to expectations obtained from the Third National Cancer Survey, San Francisco Bay Area. Two thousand four hundred biopsies were also scored by the Black-Chabou method. There is an upward trend in the breast cancer incidence as the atypia score rises, a finding which confirms conclusions from a retrospective case-control study by Black et al.