David S. Chudwin

Acquired immune dysfunction in homosexual men: immunologic profiles.

Homosexual men with Kaposi sarcoma, lymphadenopathy syndrome, opportunistic infection, and nonhomosexual traditional Kaposi sarcoma were evaluated for B cell, T cell, and complement immunity and compared to normal controls and homosexual controls. No significant immunologic abnormalities were found in the traditional Kaposi group. All homosexual groups, including the homosexual controls, had a significant decrease in the helper/suppressor cell ratio. Functional abnormalities of T-cell immunity were observed in the homosexual Kaposi sarcoma, lymphadenopathy syndrome, and opportunistic infection groups. Significant elevations of IgG, IgM, IgA, and IgE were found in the lymphadenopathy group, while only IgG and IgA were elevated in the Kaposi sarcoma group. C3, C4, and immune complexes were normal, while total hemolytic complement activity was increased in the Kaposi sarcoma and lymphadenopathy syndrome groups.

Spectrum of Sjögren syndrome in children.

Sjögren syndrome, consisting of keratoconjunctivitis sicca and xerostomia with or without another autoimmune disease, is uncommon in children. We describe our retrospective experience with eight pediatric patients with SS. All had recurrent parotid enlargement and abnormal salivary gland biopsies, six had keratoconjunctivitis sicca, and five had other autoimmune manifestations, although only two of these had other clearly defined autoimmune disorders (mixed connective tissue disease and hypergammaglobulinemic purpura). Our patients had a higher incidence of primary SS, parotid enlargement, and hematologic abnormalities than did children previously reported with SS. Children with SS demonstrate a clinical heterogeneity comparable to that seen in adults.

Patients with abnormal proportions of T-lymphocyte subsets have reduced in vitro cellular immunity

Monoclonal antibodies which identify helper/inducer (OKT4) and cytotoxic/suppressor (OKT8) subsets of human T lymphocytes have recently been used to investigate immunoregulation in isolated cell populations, as well as in human disease states. However, the relationship between relative proportions of OKT4- and OKT8-positive blood lymphocytes and in vitro cellular immune function in patients with immunodeficiencies has not been studied extensively. We enumerated T-lymphocyte subsets with OKT4 and OKT8 antibodies, and measured proliferative responses to allogeneic cells in mixed lymphocyte culture (MLC) and to phytohemagglutinin (PHA), in peripheral blood mononuclear cells (PBMCs) from 60 patients with varying degrees of immunodeficiency and 20 healthy controls. Controls had 56.0 +/- 5.3% (mean +/- 1SD) OKT4-positive lymphocytes, 28.6 +/- 5.9% OKT8-positive lymphocytes, and an OKT4/8 ratio of 2.05 +/- 0.55. We defined as abnormal values of less than 40% OKT4-positive or greater than 45% OKT8-positive lymphocytes (3 SD below and above mean values, respectively), or an OKT4/8 ratio of less than 1.2. Patients with these abnormal percentages of T-lymphocyte subsets had significantly lower mean MLC and PHA responses (P less than 0.001), and higher incidences of abnormal MLC and PHA responses (P less than 0.01). Abnormal proportions of T-lymphocyte subsets correlated with low MLC and PHA responses in most immunodeficient patients, although some patients with low MLC and PHA responses had normal subset distributions. T-Cell subset proportions were heterogeneous among patients with the same diagnosis.

ASPERGILLUS PNEUMONIA IN CHRONIC GRANULOMATOUS DISEASE: RECURRENCE AND LONG‐TERM OUTCOME

ABSTRACT. Four of 13 patients followed with chronic granulomatous disease (CGD) developed biopsy‐proven Aspergillus pneumonia. Two patients died of disseminated aspergillosis despite intensive treatment; delays in diagnosis appear to have been a major contributing cause. Two patients survived two episodes each of Aspergillus pneumonia, three and six years apart. At 12 and 18 years of age, both are well and active, although their chest X‐rays show residual scarring and pulmonary function tests indicate obstructive lung disease. These cases demonstrate that in patients with CGD, 1) multiple episodes of Aspergillus pneumonia can occur; 2) effective immunity to the organism does not develop after infection; and 3) some survivors of Aspergillus pneumonia experience only minimal morbidity.

Clinical and laboratory findings in childhoodmixed connective tissue disease: Presence of antibody to ribonucleoprotein containing the small nuclear ribonucleic acid U1

Seven children and adolescents are described with mixed connective tissue disease. The patients had varying clinical features, commonly characterized by Raynaud phenomenon, arthritis, abnormal pulmonary function, and esophageal dysmotility. All patients had speckled antinuclear antibodies and high titers (greater than 1:100,000) of antibodies to ribonuclease-sensitive extractable nuclear antigen. We prepared extractable nuclear material from radioactively labeled HeLa cells, analogous to classic extractable nuclear antigen. Sera from all seven patients precipitated ribonucleoprotein containing the small nuclear ribonucleic acid species U1 from the HeLa cell extract. Antibody to U1 ribonucleoprotein was not found in sera from 51 of 53 children and adults having a variety of autoimmune and other diseases, nor in sera from nine normal individuals. The U1 ribonucleoprotein appears to be the component of extractable nuclear antigen characteristically reacting with sera from patients with mixed connective tissue disease. The finding of a distinct molecular marker in all children studied with mixed connective tissue disease indicates that this is a distinct disease entity and not a heterogeneous population of immune disorders.

Maternal transmission of acquired immune deficiency syndrome

Acquired immune deficiency syndrome (AIDS) has been reported in previously healthy homosexual or bisexual males, intravenous drug users, heterosexual men with hemophilia, and Haitians. The finding of heterosexual hemophiliacs with AIDS has raised the possibility of a transmittable blood-borne agent as a cause of this disease. We have found three female half-siblings who had clinical and laboratory evidence for AIDS. All three had evidence of abnormal in vitro cellular immunity; two had chronic active Epstein-Barr virus infection and lymphadenopathy; all three had chronic cutaneous Candida sp infection; and two had Pneumocystis carinii pneumonia. Their mother is a prostitute/drug addict with abnormal T-cell immunity including clinical and laboratory findings of mucocutaneous candidiasis. Histocompatibility typing is consistent with the history of different fathers for each child. Immunologic studies in one child evaluated prospectively from birth were abnormal by 2 months of age. These findings and the clinical histories indicate AIDS and strongly suggest vertical transmission of an agent(s) during the perinatal period.

Effect of Antibody Concentration on Opsonic Requirements for Phagocytosis in Vitro of Streptococcus pneumoniae Types 7 and 19

Abstract We investigated the effect of the concentration of type-specific antibody to pneumococcal polysaccharide (PPS) on opsonic requirements for phagocytosis in vitro of Streptococcus pneumonia types 7 and 19. We measured the uptake by human neutrophils of radiolabeled S. pneumoniae opsonized with either complement-intact, complement-depleted (by heat inactivation), or alternative complement pathway-activated (by magnesium dichloride-ethylene glycol tetraacetic acid (MgEGTA) chelation) immune sera with varying concentrations of antibody from individuals immunized with polyvalent PPS vaccine. Increased opsonization was found with increasing concentrations of type-specific antibody in the sera. Higher concentrations of antibody were required to opsonize type 7 than type 19 bacteria, both in the presence and absence of complement activity. Type 19 bacteria were more efficiently opsonized via the alternative complement pathway than type 7. For both types, antibody and the alternative complement pathway provided most of the opsonic activity in sera with lower concentrations of type-specific antibody. At high antibody concentrations, effective opsonization occurred in heat-activated sera, indicating the requirement for complement could be overcome with sufficient amounts of antibody alone.

Increased serum opsonic activity and antibody concentration in patients with sickle cell disease after pneumococcal polysaccharide immunization

Opsonic defects have been reported in unimmunized patients with sickle cell disease. We found significant increases (P less than 0.001) in serum opsonic activity, measured by a radiolabeled bacterial uptake assay, and in type 7 pneumococcal polysaccharide antibody concentration in 17 such patients 2 years of age or older after pneumococcal polysaccharide immunization. All 17 patients and six healthy controls achieved a type 7 antibody concentration of more than 300 ng antibody nitrogen per milliliter, believed to be the protective level of antibody in vivo. Six patients with sickle cell disease less than 2 years of age did not have a significant increase in type 7 antibody concentration after immunization. Only three of these six patients achieved a postimmunization type 7 antibody concentration exceeding 300 ng Ab N/ml. Overall, 16 of 23 patients with sickle cell disease (70%) had a twofold or greater increase in type 7 antibody concentration, and 13 of these (81%) had a corresponding increase in opsonic activity (P less than 0.001). Thus most patients who responded to pneumococcal polysaccharide immunization had a concurrent increase in opsonic activity in vitro.

Response of agranulocytosis to prolonged antithymocyte globulin therapy.

A girl with a history of autoimmune disease developed life-threatening agranulocytosis. A bone marrow biopsy demonstrated selective granulocytic hypoplasia. No antineutrophil antibodies were found. In vitro bone marrow culture of granulocytic progenitor cells suggested T cell-mediated inhibition of colony formation, which was reduced by in vitro treatment of marrow cells with either hydrocortisone or an antibody directed against T-lymphocytes and complement. The patient responded to treatment with antithymocyte globulin after administration of corticosteroids and other immunosuppressants failed to increase her neutrophil count significantly. Attempts to stop ATG treatment resulted in precipitous drops in her neutrophil counts, which reversed with readministration of ATG. She then received weekly ATG infusions for over 24 months until she was able to maintain a normal neutrophil count. A trial of ATG therapy may be indicated in severe neutropenia when in vitro culture results indicate a possible autoimmune basis.

905 CHILDHOOD MIXED CONNECTIVE TISSUE DISEASE

We reviewed the clinical and laboratory features of 6 children with MCTD (4 girls, 2 boys). Initial symptoms (mean age of onset 9.2 years) were arthritis (2), chronic fevers (2), and urticaria and Raynauds phenomenon (2). Mean age at diagnosis was 14.2 years. Clinical features included:There has been no mortality, but 3/6 are significantly disabled (mean followup of 3.4 years) despite treatment with sallcylates, prednisone and in 3 patients chlorambucil. Our experience with MCTD in children reflects greater chronic morbidity than reported in adults.