Israel Medical Association Journal

The major autoantigens in the inflamed synovium in rheumatoid arthritis (RA) are citrullinated peptides. Citrullinated peptides are employed in diagnostic kits for detection of anti-citrullinated protein antibodies (ACPA), a serological marker with high specificity and sensitivity in the diagnosis of RA, and have been included in the new ACR/EULAR classification criteria for RA. ACPA-positive RA patients suffer from an erosive and more aggressive disease compared to ACPA-negative patients. In view of the mounting indications that ACPA plays a seminal role in the pathogenesis of RA, it might be valuable to pursue a specific treatment aiming ACPA as a target. We found that citrullinated peptides, which contain a unique amino acid, citrulline, alter the protein structure within the connective tissue, leading to tolerance breakdown and triggering the autoimmune response in RA. However, with different doses and routes of administration, citrullinated peptides can promote immune tolerance rather than induction of disease. 

Background: In the last two decades milk oral immunotherapy has gained interest as an effective treatment option for milk-allergic patients.

Objectives: To report on the efficacy of a milk oral immunotherapy.

Methods: Children with immunoglobulin E-mediated cow’s milk allergy were included in the protocol. The treatment consisted of an induction phase in which milk doses were increased weekly in the hospital, while the tolerated dose was continued daily at home. The goal was to achieve a minimum milk intake of 200 ml a day. During the maintenance phase, patients ingested at least 200 ml of milk in a single dose every day.

Results: The protocol was applied to 105 milk-allergic children diagnosed by specific IgE to milk and controlled oral food challenge. The mean duration of the induction phase was 19 weeks. Of the 105 subjects, 86 (81.9%) successfully complied with the protocol and 19 (19.1%) failed. Causes of failure were moderate/severe reactions in 12 patients (12.44%) and personal reasons in 7 (6.66%). A total of 182 adverse reactions occurred during the induction phase, most of them mild. Baseline specific IgE to milk and casein were significantly lower (P < 0.05) in the successfully treated group compared to the group in which the treatment failed.

Conclusions: Milk oral immunotherapy is a safe and effective treatment for milk-allergic children, although adverse reactions may occur. Baseline milk and casein-specific IgE may be useful to predict a good response to milk oral immunotherapy.

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[1] IgE = immunoglobulin E

Background: Feeding neonates with humanized milk formula in maternity hospitals may increase the prevalence of milk allergy in infants. However, prospective studies of the possible allergenic effect of very early soy-based formula feeding are lacking.

Objectives: To assess the prevalence of soy allergy in infants fed soy-based formula in the first 3 days of life.

Methods: The study group included 982 healthy full-term infants born within a 7 month period at a hospital that routinely uses soy-based formula to supplement breastfeeding. In-hospital feeding was recorded and the parents were interviewed once monthly over the next 6 months regarding feeding practices and clinical symptoms suggesting soy allergy in the infant.

Results: Ninety-nine percent of the infants received soy-based formula supplement in hospital, and 33–42% at home. No cases of immediate allergic reaction to soy or soy-induced enterocolitis were reported.

Conclusions: The use of soy-based formula in the early neonatal period does not apparently increase the prevalence of soy allergy in infants followed for the next 6 months.

Background: Type 2 diabetes, an extreme state of glucose intolerance, has been found to be associated with cancer mortality; less is known about impaired glucose tolerance and cancer incidence.

Objectives: To examine the association between fasting and post-load plasma glucose and insulin, and the 20 year incidence of cancer.

Methods: We followed a sample of the Jewish Israeli population (n=2780), free of cancer at baseline,

from 1977-1980 to 1999 for cancer incidence and mortality. Baseline fasting and 1 and 2 hour post-load plasma glucose levels were recorded, as was insulin in 1797 of them.

Results: During 20 years, 329 individuals (11.8%) developed cancer. Cancer incidence for all sites differed between men and women (13.0% and 10.7%, P = 0.03), and among different glucose tolerance status groups (P = 0.01). Cancer incidence hazard ratio, by glucose status adjusted for gender, age, ethnicity, smoking and body mass index, was 1.24 (95%CI 0.96–1.62, P = 0.10) for impaired fasting glucose or impaired glucose tolerance, and 1.32 (95%CI 0.96–1.81, P = 0.09) for type 2 diabetes mellitus, compared to those who were normoglycemic at baseline. Fasting insulin and cancer incidence were not associated.

Conclusions: An increased long-term cancer risk for individuals with impaired fasting glucose or glucose tolerance, or diabetes, is suggested. Even this modest association could have substantial public health consequences.
 

Objectives: To assess the prevalence of metabolic syndrome and different glucose intolerance states in healthy, overweight Arab individuals attending a primary healthcare clinic in Israel.

Methods: We randomly recruited 95 subjects attending a primary healthcare clinic who were healthy, overweight (body mass index >27) and above the age of 40. Medical and family history was obtained and anthropometric parameters measured. Blood chemistry and oral glucose tolerance test were performed after overnight fasting.

Results: Twenty-seven percent of the subjects tested had undiagnosed type 2 diabetes according to WHO criteria, 42% had impaired fasting glucose and/or impaired glucose tolerance and only 31% had a normal OGTT[1]. Metabolic syndrome was found in 48% according to criteria of the U.S. National Cholesterol Education Program, with direct correlation of this condition with BMI[2] and insulin resistance calculated by homeostasis model assessment. Subjects with metabolic syndrome had a higher risk for abnormality in glucose metabolism, and the more metabolic syndrome components the subject had the higher was the risk for abnormal glucose metabolism. Metabolic syndrome predicted the result of OGTT with 0.67 sensitivity and 0.78 specificity. When combined with IFG[3], sensitivity was 0.83 and specificity 0.86 for predicting the OGTT result.

Conclusions: According to our initial evaluation approximately 70% of the overweight Arab population in Israel has either metabolic syndrome or abnormal glucose metabolism, indicating that they are at high risk to develop type 2 diabetes and cardiovascular morbidity and mortality. This population is likely to benefit from an intervention program.

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[1] OGTT = oral glucose tolerance test

[2] BMI = body mass index

[3] IFG = impaired fasting glucose