Susanna Cunningham-Rundles

An outbreak of community-acquired Pneumocystis carinii pneumonia. Initial manifestation of cellular immune dysfunction.

Eleven cases of community-acquired Pneumocystis carinii pneumonia occurred between 1979 and 1981 and prompted clinical and immunologic evaluation of the patients. Young men who were drug abusers (seven patients), homosexuals (six), or both (two) presented with pneumonia. Immunologic testing revealed that absolute lymphocyte counts, T-cell counts, and lymphocyte proliferation were depressed, and that humoral immunity was intact. Of the 11 patients, one was found to have Kaposis sarcoma, and another had angioimmunoblastic lymphadenopathy. Eight patients died. In the remaining three, no diagnosis of an immunosuppressive disease was established, despite persistence of immune defects. These cases of pneumocystosis suggest the importance of cell-mediated immune function in the defense against P. carinii. The occurrence of this infection among drug abusers and homosexuals indicates that these groups may be at high risk for this infection.

Preliminary Observations on the Effect of Recombinant Leukocyte a Interferon in Homosexual Men with Kaposi's Sarcoma

Preliminary clinical trials have shown that both natural and recombinant-DNA-produced human interferons are occasionally capable of inhibiting the growth of some tumors.1 2 3 4 Although the tumors ...

The efficacy and safety of B‐cell depletion with anti‐CD20 monoclonal antibody in adults with chronic immune thrombocytopenic purpura

Because of its B‐cell depleting effect, rituximab has entered clinical trials in several autoimmune conditions. This study assesses the efficacy and safety of rituximab in 57 adults with chronic immune thrombocytopenic purpura (ITP). All patients had platelet counts <30 × 109/l, all had received two or more previous ITP treatments and 31 had undergone splenectomy. Patients received rituximab 375 mg/m2 weekly for 4 weeks. Thirty‐one patients (54%) responded, achieving a platelet count >50 × 109/l: 18 achieved a complete response (CR: platelet count >150 × 109/l) and 13 a partial response (PR: platelet count 50–150 × 109/l). Twenty‐nine responses occurred within 8 weeks of the first infusion. Sixteen of 18 CR patients (28% overall), including eight who had failed splenectomy, continued in CR after a median of 72·5 weeks; 15 of 16 are >1 year from the first infusion. Only two of 13 maintained a PR. Thirty‐three patients experienced grade 1–2 adverse events and one a grade 3 event, but they all completed treatment. Circulating B cells fell to <0·03 × 109/l. No changes in immunoglobulin levels or infectious complications were seen. In summary, rituximab was well tolerated with no immediate complications and induced a lasting, substantial response in 32% of adults with chronic ITP.

Generalized Lymphadenopathy in Homosexual Men

The cases of 90 homosexual or bisexual men with generalized lymphadenopathy were studied by epidemiologic, clinical, pathologic, immunologic, and genetic methods. The patients ranged in age from 20 to 52 years and had histories of multiple sexually transmitted diseases and both recreational and prescription drug use. Histologically, their lymph nodes showed three patterns: explosive follicular hyperplasia; follicular involution with expansion of the paracortical area; and a mixed pattern of follicular hyperplasia and follicular involution in the same lymph node. The frequency of HLA-DR5 was significantly increased in these patients (p less than 0.005) compared with that in controls. All patients had impaired cell-mediated immunity. Opportunistic infections, lymphomas, or Kaposis sarcoma subsequently developed in 15 patients who had had severe immune dysfunction for the previous 3 to 13 months. We suggest that generalized lymphadenopathy is part of the spectrum of a disorder manifested by acquired immunodeficiency, opportunistic infections, Kaposis sarcoma, and malignant lymphomas.

The Natural History of Kaposi's Sarcoma in the Acquired Immunodeficiency Syndrome

Kaposis sarcoma is a multifocal systemic neoplasm histologically characterized by proliferating fibroblastic and microvascular elements. Initial signs include macules, papules, or nodules on the skin or mucosal surface. Lesions are frequently found on the trunk, arms, and head and neck. In general, sites of involvement and tumor load do not correlate with prognosis. A general decrease in the functional capacities of T and B cells is found in most patients. Kaposis sarcoma is reported as the initial manifestation of the acquired immunodeficiency syndrome (AIDS) in approximately 30% of cases. Most cases are in men, although it has been reported in all risk groups. Kaposis sarcoma in AIDS is more frequent among whites and homosexuals than blacks and intravenous drug abusers. Overall mortality is approximately 41%, with over 60% of patients alive at 1 year and 50% at 22 months. Overall survival is 18 months; however, some patients who have had the disease for 3 to 4 years are still doing well.

Incidence of cancer in 98 patients with common varied immunodeficiency

Ninety-eight patients with common varied immunodeficiency have been observed for periods of 1–13 years. In 1986, 78 were alive, 19 had died, and 1 could not be located. Eleven patients in the group had developed cancer; two patients had had two cancers. Of the total number of neoplastic malignancies, seven were non-Hodgkins lymphoma, one patient had a Waldenstroms macroglobulinemia, and nine of the patients who developed cancer were female. Cancer developed in the fifth or sixth decade of life for 10 of the 11 patients. These data show an 8- to 13-fold increase in cancer in general for patients who have this immunodeficiency and a 438-fold increase in lymphoma for females.

Outcomes 5 years after response to rituximab therapy in children and adults with immune thrombocytopenia.

Treatments for immune thrombocytopenic purpura (ITP) providing durable platelet responses without continued dosing are limited. Whereas complete responses (CRs) to B-cell depletion in ITP usually last for 1 year in adults, partial responses (PRs) are less durable. Comparable data do not exist for children and 5-year outcomes are unavailable. Patients with ITP treated with rituximab who achieved CRs and PRs (platelets > 150 × 10(9)/L or 50-150 × 10(9)/L, respectively) were selected to be assessed for duration of their response; 72 adults whose response lasted at least 1 year and 66 children with response of any duration were included. Patients had baseline platelet counts < 30 × 10(9)/L; 95% had ITP of > 6 months in duration. Adults and children each had initial overall response rates of 57% and similar 5-year estimates of persisting response (21% and 26%, respectively). Children did not relapse after 2 years from initial treatment whereas adults did. Initial CR and prolonged B-cell depletion predicted sustained responses whereas prior splenectomy, age, sex, and duration of ITP did not. No novel or substantial long-term clinical toxicity was observed. In summary, 21% to 26% of adults and children with chronic ITP treated with standard-dose rituximab maintained a treatment-free response for at least 5 years without major toxicity. These results can inform clinical decision-making.

Efficacy of Intravenous Immunoglobulin in Primary Humoral Immunodeficiency Disease

Twenty-one patients with primary humoral immunodeficiency were treated for 1 year with a chemically intact immunoglobulin, 300 mg/kg body weight given intravenously every 3 weeks, to compare immunoglobulin levels and clinical status with results achieved after standard treatment with intramuscular immunoglobulin given previously for 1 year. A substantial reduction of specific acute illnesses and antibiotic use was found for 18 of the 21 patients, particularly during the second 6 months of treatment. Average IgG levels before intravenous infusion were increased 243 mg/dL over previous intramuscular pre-injection levels. Adverse effects were recorded for 2.5% of infusions.

Opportunistic Infection in Previously Healthy Women: Initial Manifestations of a Community-Acquired Cellular Immunodeficiency

Opportunistic infections and unusual tumors have been reported in an unprecedented outbreak of community-acquired cellular immune deficiency among homosexual and drug-abusing men. We report five women with the same syndrome. The women were residents of metropolitan New York City closely associated with drug abuse either by personal use (our patients) or close sexual contact with an abuser (one patient). One patient was bisexual. All five patients developed Pneumocystis carinii pneumonia as well as combinations of other opportunistic infections including oral candida, disseminated mycobacteria, and ulcerative herpes simplex infections. All patients had marked depression of cellular immune function. Three patients died. The appearance of this syndrome in women has important implications with regard to the epidemiology and etiology of this emerging syndrome.

Probiotics and immune response

Current evidence supports the concept that oral administration of probiotic lactobacilli may be therapeutic in preventing antibiotic-associated diarrhea in children and in reestablishing normal flora in the gastrointestinal tract. Children with human immunodeficiency virus (HIV) infections may have episodes of diarrhea and frequently experience malabsorption associated with possible bacterial overgrowth; together these may interact to produce the growth abnormalities characteristic of this group. The overall objective of this investigation has been to determine whether oral administration of the probiotic Lactobacillus plantarum 299v could improve nutrient status and promote growth in children congenitally exposed to HIV. In addition, the possible beneficial effect of Lactobacillus plantarum 299v in modulating immune response was evaluated. In preliminary results described here, we report on the ability of Lactobacillus plantarum 299v to colonize children with HIV and to elicit specific systemic immune response after oral supplementation.