Allen Litwin

Occupational asthma induced by inhalation and ingestion of garlic

Repeated exposure to garlic dust induced severe asthma in an atopic patient. Subsequently, the patient also developed marked adverse responses after ingestion of garlic. Immunologic investigations carried out in an asymptomatic period revealed significant skin reactivity and bronchospasm after challenge with both garlic dust and extract. The results of a controlled oral challenge test to garlic dust were also positive. The patients serum contained unusually high quantities of garlic-specific IgE. Cross allergenicity between garlic and other members of the Liliaceae family were documented by the RAST inhibition technique.

Oral immunotherapy with short ragweed extract in a novel encapsulated preparation: A double-blind study

BACKGROUND In the past, oral immunotherapy with allergens has had limited clinical effectiveness, presumably because of gastrointestinal destruction of allergens. OBJECTIVE We have developed a new technique for microencapsulating protein antigens that permits them, when given orally, to bypass the stomach and be delivered to the small intestine in a highly immunogenic form. This studys purpose was to confirm the immunologic potency of orally administered short ragweed pollen extracts (SRW) microencapsulated (mSRW) by this new technique and to study the effectiveness of mSRW in controlling the symptoms of ragweed-induced hay fever. METHODS Twenty-one SRW-sensitive patients were treated with mSRW in a double-blind placebo-controlled study. Serum SRW IgG and IgE antibodies and nasal secretory IgA antibodies were determined. During the ragweed season, symptoms were quantified by symptom-medication scoring. RESULTS The treated patients had high titers of serum SRW IgG antibodies (1.15 microg/ml at baseline, increasing to 21.21 microg/ml), experienced regulation of the seasonal increase in serum SRW IgE antibodies (+9% vs +59% in placebo-treated patients), and produced a small amount of nasal SRW IgA antibodies. Despite an insubstantial pollen count, the symptom-medication scores in the treated group were lower than those in the placebo group (4.28 vs 6.18, p = 0.059), but the differences were statistically significant only in the subgroup that tolerated high doses (>20 microg of Amb a 1 in 19 of 21 patients, p = 0.04). These effects were accomplished without inducing any systemic reactions with a dose of mSRW (mean, 23.8 microg of Amb a 1) only slightly higher than that used in high-dose subcutaneous immunotherapy. CONCLUSION Oral mSRW seems a safe, easily administered, and immunologically potent treatment for ragweed-induced hay fever, but its ultimate utility requires further study.

Cellular Immunity to Nuclear Antigens in Systemic Lupus Erythematosus

Cellular immune repsonses were determined by skin testing and mitogen- and antigen-induced blastic transformation of peripheral blood lymphocyte cultures in 24 patients with systemic lupus erythematosus (SLE) and 24 normal subjects. The incidence of positive skin tests with Candida albicans, PPD (tuberculin-purified protein derivative) intermediate strength, Trichophyton and histoplasmin was not significantly different in the two groups nor was lymphocyte stimulation by the mitogen phytohemagglutinin-M (PHA-M), implying that cellular immunity is normal in SLE. However, the SLE patients had a significantly increased incidence of positive skin tests and stimulated lymphocyte cultures to a number of nuclear antigens compared with normal subjects. No correlation could be made between the test results and the activity of the SLE at the time of study except for a significant association between lymphocyte culture stimulation by rabbit thymus native DNA and active SLE nephritis. Patients with a membranous antinuclear factor (ANF) pattern had positive skin tests with rabbit thymus native DNA and usually had active disease.

Induction of antibodies to nuclear antigens in rabbits by immunization with hydralazine-human serum albumin conjugates.

The antihypertensive drug hydralazine can induce in man a syndrome similar to spontaneous systemic lupus erythematosus (SLE). The pathogenesis of this drug-induced syndrome is not understood. In this investigation, five groups of rabbits were studied: group I, 10 rabbits hyperimmunized with hydralazine conjugated to human serum albumin (HSA) in complete Freunds adjuvant (CFA); group II, four rabbits with HSA in CFA; group III, four rabbits with CFA alone; group IV, five rabbits with hydralazine conjugated to rabbit serum albumin (RSA); and group V, four rabbits with a major metabolite of hydralazine conjugated to HSA. The rabbits immunized with hydralazine-HSA developed rising titers of antibodies to hydralazine and progressively increasing amounts of antibodies to both single-stranded and native DNA. The antibodies to DNA were cross-reactive with hydralazine as determined by inhibition of DNA binding and DNA hemagglutination tests. Similar results were obtained in rabbits immunized with the metabolite-HSA compound except the major hapten antibody response was to the metabolite. The DNA antibodies in this group were also capable of being absorbed by metabolite-HSA as well as hydralazine-HSA, indicative of the cross-reactivity between hydralazine and its metabolite. Immunization with hydralazine-RSA caused rabbits to produce antibodies to hydralazine but not to DNA, indicating the requirement for an immune response to the carrier protein in order for antibodies reactive with DNA to be produced. Thus, hyperimmunization of rabbits with hydralazine-protein conjugates may provide a useful animal model of SLE. The data suggests that an immune response to hydralazine may be important in human hydralazine-induced SLE.

Immunologic Effects of Encapsulated Short Ragweed Extract: a Potent New Agent for Oral Immunotherapy

BACKGROUND Oral allergen immunotherapy with conventional allergens has not been a useful mode of treatment because of the lack of potency of allergens when administered by this route. OBJECTIVE To study the immunologic potency of short ragweed pollen extracts microencapsulated by a new technique administered orally to short ragweed pollen-sensitive humans and to establish the dose of oral microencapsulated short ragweed pollen extract required for these effects. METHODS Nine short ragweed pollen-sensitive patients were treated with a new oral agent for immunotherapy, microencapsulated short ragweed pollen extract, in an open study. The effectiveness of this treatment was determined by comparison to a group of nine matched short ragweed pollen-sensitive patients who received no treatment. Treated patients developed high titers of short ragweed-specific IgG and IgE antibodies and their expected seasonal increase in IgE antibodies was regulated. The dose of microencapsulated short ragweed pollen extract required to achieve these effects was only slightly higher than the dose of short ragweed pollen extract used in high dose subcutaneous immunotherapy. Furthermore, this dose was achieved in 7 weeks. There were no side effects other than mild gastrointestinal ones. The nine treated patients fared clinically better during the ragweed season than the untreated patients in this open study. CONCLUSION This study suggests that allergens microencapsulated by this new technique may make oral immunotherapy a practical mode of treatment.

Prospective study of immunologic effects of hydralazine in hypertensive patients

Twenty‐seven hypertensive patients (23 of whom were black) were treated with hydralazine as their major antihypertensive drug and were followed for evidence of autoimmunity and clinical systemic lupus erythematosus (SLE). Only one patient developed SLE but many, although asymptomatic, had serologic evidence of autoimmunity: antibodies to single‐ and double‐stranded ribonucleic acid (RNA), single‐stranded deoxyribonucleic acid (DNA), histones, and lymphocytes. Acetylation phenotype profoundly influenced this response; slow acetylators had a higher incidence and larger amounts of autoantibodies. Antibodies to both types of RNA were a more sensitive index of autoimmunity than antinuclear antibodies. Hydralazine treatment did not alter cell‐mediated immune responses. The hydralazine SLE patient had large amounts of autoantibodies that were predominantly IgG, while in the others IgM autoantibodies were predominant. No antibodies, but positive lymphoproliferative responses to hydralazine, were found in half the patients tested.

Modulation of the immune response to ragweed allergens by peptic fragments

Fragments of short ragweed extract were prepared by peptic digestion and fractionated by molecular exclusion chromatography. We focused on fragmenting a ragweed fraction that was enriched for Amb a I. Digestion products in the molecular weight range of 5–15 kD (fSRW) were examined for their antigenic, immunogenic and immunosuppressive properties. fSRW was poorly immunogenic and unable to induce ragweed‐specific PCA reactions in rat skin or to bind to anti‐ragweed IgG antibodies. Intravenous administration of fSRW either prior to or after intraperitoneal immunization with a ragweed preparation resulted in a significant suppression of the immune response. T cells isolated from lymph nodes of mice immunized with ragweed were stimulated by fSRW in a lymphoproliferation assay. Moreover, T cells from mice injected with fSRW were immunosuppressive when transferred into mice immunized with intact ragweed antigens. Our data demonstrate that peptic fragments (fSRW) of ragweed lack B‐cell determinants while retaining their T‐cell immunoregulatory properties. Potentially these peptides are less likely to cause adverse reactions in allergen sensitive patients and thus offer a new approach to allergen immunotherapy.

Drug-Related Rheumatic Diseases

The most important and most common drug-related rheumatic disease is drug-related lupus. The first case of a probable drug-related lupus (DRL) was described by Hoffman (1945) and incriminated the antibiotic sulfadiazine. Other reports during the 1950s related to other sulfonamides and penicillin. It is possible that these were accidental occurrences or that the patients had idiopathic systemic lupus erythematosus (SLE).