Charles H. Kirkpatrick

Activities and characteristics of transfer factors

This report summarizes three components of our transfer factor research program. Several clinical studies have used oral administration of transfer factor containing materials. Sceptics have rejected these findings by assuming that the acidic and enzymatic environment of the gastrointestinal tract would destroy the factors. To further examine this issue, we have conducted dose-response studies of the delayed-type hypersensitivity reaction in mice that were given transfer factor either by gavage or subcutaneously. There were no difference in the responses that were related to the route of administration. We conclude that oral route of administration is efficacious and should be used when possible.We have also studied the effects of transfer factors on immune responses by recipients. The details of this research are presented in the paper by Dr. Alvarez-Thull. Briefly, the study showed that recipients of a specific transfer factor responded to the antigen for which the factor was specific by secreting gamma-IFN, but no other cytokines.The structures of transfer factor molecules are unknown. We have developed a process for isolating transfer factors in pure form and we have obtained preliminary data concerning amino acid sequences. Our goal is to obtain the complete primary structure of several transfer factor molecules.

Profiles of cytokine production in recipients of transfer factors

Transfer factors (TF) are proteins that transfer the ability to express cell-mediated immunity from immune donors to non-immune recipients. The mechanisms of these effects have not been defined. The experiments described in this report were undertaken to test the hypothesis that a mechanism through which the beneficial effects of TF are expressed in clinical situation is through “education” of the immune system to produce certain cytokines in response to antigenic stimulation.BALB/c mice were sensitized to Herpes simplexvirus (HSV) either by sublethal systemic or cutaneous infections by administration of a HSV-specific TF. One week later their spleen cells were collected and single cell suspensions were stimulated in vitro with irradiated HSV or concanavalin A. Culture supernatants were collected and assayed for content of IL-2, IL-4, IL-10 and IFN-g.Spleen cells from infected mice responded to concanavalin A and to HSV by secreting large amounts of IL-2 and IFN-g, modest amounts of IL-10, and no IL-4. Transfer factor recipients produced similar cytokine profiles in response to concavalin A. These mice, however, responded to HSV by secreting IFN-g, but no IL-2. Thus, TF treatment selectively affects cytokine production in response to antigenic stimulation.

Progressive immunodeficiency in a patient with IgA deficiency.

HISTORY OF PRESENT ILLNESS A 31-year-old white woman with a history of IgA deficiency and deletion of the long arm of chromosome 18 was referred to the Allergy-Immunology Clinic for evaluation of recent onset pruritic, erythematous papular lesions over her chest and antecubital fossae. These had developed several months prior to our evaluation and were accompanied by a lesion on her hard palate, which had been biopsied and reportedly showed invasive hyphal forms consistent with Candida albicans. An additional dermatologic manifestation included progressive vitiligo since childhood. Recent symptoms also included a 7-month history of dysphagia. This began as dysphagia for liquids but evolved to include solids as well as medications. It was accompanied by retrosternal chest discomfort. She had lost 22 pounds. There was no recent history of nausea, vomiting, or diarrhea. Respiratory symptoms included intermittent dyspnea that would subside without treatment. She also complained of chronic sore throat and postnasal drainage that were being treated with amoxicillin and intranasal fluticasone. There was no history of recurrent pneumonia. Her past medical history was significant for IgA deficiency and deletion of the long arm of chromosome 18.1 She had experienced frequent respiratory infections until age 18 months and recurrent urinary tract infections that were associated with bilateral reflux and hypotonic bladder. The frequency of bladder infections decreased after bilateral ureteral implantations. An initial immunologic evaluation at age 4 years in 1969 revealed an undetectable IgA level, IgM 155 mg/dL (normal range 50 18), and IgG 1000 mg/dL (normal range 929 228). Delayed type hypersensitivity was normal (Table 1). Her serum contained hemagglutinating antibodies for diphtheria and tetanus and a Schick test was negative (no erythema at the site of toxin injection). In 1972, at age 7 years, she had idiopathic thrombocytopenia which was treated with corticosteroids and platelet transfusions. At approximately age 20 years, she developed diarrhea which persisted for several years. An exhaustive laboratory evaluation revealed Giardia lamblia in the stool and treatment with appropriate antibiotics resulted in the resolution of these symptoms. Her family history was significant in that immunoglobulin evaluation of both parents and a sibling were normal. Chromosomal analysis of both parents was also normal. Social history was negative for tobacco, ethanol, and intravenous drug abuse. There was, however, possible sexual contact with an intravenous drug user. The physical examination revealed a slender woman with a flat face and closely approximated features. Her pulse rate, blood pressure, and temperature were normal. Examination of the head and neck revealed tortuous external auditory canals, purulent nasal and postnasal drainage, severe gingivitis, and patchy candidiasis of the buccal mucosa. There was a 3 3-cm granulomatous-appearing nontender mass on the hard palate. There was no hepatosplenomegaly or palpable lymphadenopathy. Examination of the extremities revealed no cyanosis, clubbing, or edema. There was no evidence of active or past fungal infection of the nails. Skin examination was remarkable for vitiligo of the arms and chest and multiple 2 3 to 3 5 mm erythematous papules in the antecubital fossae and on the chest. The skin lesions were not tender and none of them was pustular. The surface of each lesion was somewhat scaly. Deep tendon reflexes were normal. A pelvic examination was not done. The remainder of the physical examination was normal. Current medications included topical nystatin, intranasal fluticasone, and amoxicillin. She had not used a systemic antifungal drug.

Common variable immunodeficiency presenting as herpes simplex virus encephalitis

Common variable immunodeficiency (CVID) is a disorder in which patients are unusually susceptible to infections with encapsulated bacteria. Here we describe three adults with CVID in whom the correct diagnosis was not reached until they had Herpes simplex encephalitis. Failure to identify the underlying immune deficiency likely contributed to these debilitating infections.

A man with multiple infections with unusual organisms

per lobes and a fungus ball in the left upper lobe (Fig 1). A bronchoscopy specimen grew Actinomyces and Aspergillus species. He was treated with doxycycline (the patient was allergic to penicillin) and amphotericin B. Neither of these organisms grew from a bronchoscopic specimen obtained in December 1996. During the course of treatment, his fevers abated, the cough and sputum production improved, his energy level improved, and the weight loss stopped.