Israel Medical Association Journal

Background: Insulin-dependent diabetes mellitus is dominated by a Th1 response whereas atopic diseases such as asthma, eczema and allergic rhinitis are characterized by a Th2 response. Because it is known that Th1 and Th2 cells reciprocally counteract each other, it can be speculated that the prevalence of Th2-mediated diseases is lower in patients with a Th1-mediated disease.

Objectives: To compare the prevalence of atopic diseases among children with IDDM[1] and age-matched controls.

Methods: The study group comprised 65 children with IDDM attending the pediatric endocrinology clinic at the Wolfson Medical Center. The control group consisted of 74 non-diabetic children who presented at the emergency room due to an acute illness (burns, abdominal pain, fever, head trauma). Patients were asked to complete a detailed questionnaire on their history of personal and familial atopic and autoimmune diseases. In addition, a total serum immunoglobulin E concentration and the presence of IgE[2] antibodies to a panel of relevant inhalant allergens were analyzed.

Results: Children with IDDM and their first-degree relatives had a significantly higher prevalence of other autoimmune diseases such as thyroiditis and celiac as compared to controls. The two groups had a similar prevalence of atopic diseases with respect to history, total serum IgE, or the presence of IgE antibodies to a panel of relevant inhalant allergens.

Conclusions: The prevalence of atopic diseases in IDDM patients was similar to that in the normal population. Our results suggest that the traditional Th1/Th2 theory to explain the complexity of the immune response is oversimplified. 

Background: The global spread of tuberculosis necessitates the development of an effective vaccine and new treatment modalities. That requires a better understanding of the differences in regulation of the immune responses to Mycobacterium tuberculosis between individuals who are susceptible or resistant to the infection. Previous immune studies in young Ethiopian immigrants to Israel did not demonstrate anergy to purified protein derivative or a Th2-like cytokine profile.

Objectives: To evaluate the profile of Th1 and Th2 cytokine production in immigrant TB patients, in comparison with asymptomatic control subjects.

Methods: The present study included (part 1): 39 patients with acute TB[1] (group 1), 34 patients with chronic relapsing TB (group 2), 39 Mantoux-positive asymptomatic TB contacts (group 3), and 21 Mantoux-negative asymptomatic controls (group 4). Patients were mainly immigrants from Eastern Europe and Ethiopia. Levels of interferon gamma, interleukin 2 receptor, IL-6[2] and IL-10 were measured in serum and in non-stimulated and PPD[3]-stimulated peripheral blood mononuclear cell culture supernatants, using commercial ELISA kits. In addition (part 2), levels of IFNg[4] and IL-12p40 were evaluated in 31 immigrant Ethiopian patients and 58 contact family members.

Results: Patients with acute disease tended to secrete more cytokines than contacts, and contacts more than chronic patients and controls, without a specific bias. None of the patients showed in vitro anergy. Discriminant probability analysis showed that from the total of 12 available parameters, a cluster of 6 (IFNg-SER[5], IFNg-PPD, IL-2R[6]-SER, IL-10-SER, IL-10-NS[7] and IL-6-PPD) predicted an 84% probability to become a TB contact upon exposure, 71% a chronic TB patient and 61% an acute TB patient. Family-specific patterns of IFNg were demonstrated in the second part of the study.

Conclusions: Firstly, no deficiency in cytokine production was demonstrated in TB patients. Secondly, acute TB patients secreted more cytokines than contacts, and contacts more than unexposed controls. Thus, neither anergy nor a cytokine dysregulation explains susceptibility to acute TB disease in our cohort, although chronic TB patients produced less cytokines than did acute patients and less than asymptomatic contacts. Thirdly, a certain cytokine configuration may predict a trend of susceptibility to acquire, or not acquire, clinical TB. It is presently unclear whether this finding may explain the disease spread in large populations. Finally, the familial association of IFNg secretion levels probably points towards a genetic regulation of the immune response to Mycobacterium tuberculosis.