Israel Medical Association Journal

Background: The presence of anti-cyclic citrullinated peptide autoantibody is highly specific for rheumatoid arthritis. Certain HLA-DR4 (HLA-DRB1*04) alleles, also known as the "shared epitope," are associated with increased susceptibility to RA[1]. In addition, these alleles may also have relevance for disease outcome. Anti-CCP[2] antibody positivity has been associated with the presence of HLA-DR4 alleles in patients with RA. However, there is little information available regarding any relationship between quantitative anti-CCP production (serum anti-CCP concentrations) and the shared epitope.

Objectives: To determine the association between anti-CCP antibody production and various HLA-DRB1 alleles.

Methods: Serum anti-CCP, rheumatoid factor and C-reactive protein levels were assessed in 53 RA patients. All these patients underwent HLA-DRB1 genotyping.

Results: Of the 53 patients 33 (62%) were positive for anti-CCP antibody. We found significant correlations between anti-CCP and RF[3] positivity (chi-square = 6.717, P < 0.01), as well as between anti-CCP and HLA-DRB1*04 positivity (chi-square = 5.828, P < 0.01). There was no correlation between RF positivity and serum levels, CRP[4] serum levels and HLA-DRB1*04 positivity. When quantitatively comparing serum anti-CCP levels with shared epitope positivity, patients carrying one or two copies of HLA-DRB1*04 alleles had significantly higher anti-CCP concentrations (530.0 ± 182.6 U/ml) compared to DRB1*04-negative patients (56.8 ± 27.4 U/ml) (P < 0.01). There was no difference in serum anti-CCP antibody concentrations between patients carrying only one HLA-DRB1*01 allele but no HLA-DRB1*04 allele (12.0 ± 8.6 U/ml) in comparison to SE[5]-negative patients (76.8 ± 56.2 U/ml). Regarding non-SE HLA-DRB1 genotypes, all 6 patients (100%) carrying DRB1*15 alleles and 6 of 7 (85%) patients carrying DRB1*13 were anti-CCP positive. In addition, patients with HLA-DRB1*13 (282.5 ± 23.8 U/ml) and DRB1*15 (398.7 ± 76.2 U/ml) produced significantly more anti-CCP than did any other non-SE HLA-DRB1 subtypes (P < 0.01).

Conclusions: There is significant association between anti-CCP and RF, as well as between anti-CCP and SE positivity in RA. In addition, the presence of one or two copies of HLA-DRB1*04 alleles has been associated with higher serum anti-CCP antibody levels. Thus, patients carrying HLA-DRB1*04 alleles exhibited an overall tenfold increase in serum anti-CCP antibody levels in comparison to HLA-DRB1*04-negative subjects. Increased anti-CCP production may also be associated with other non-SE HLA-DRB1 genotypes, such as DRB1*13 or DRB1*15. In reports by other investigators, both anti-CCP concentrations

Among the several mechanisms that play a role in maintaining peripheral self-tolerance is the existence of a unique CD4+CD25+ population of naturally occurring regulatory T cells, which actively prevent both the activation and the effector function of autoreactive T cells that have escaped different mechanisms of tolerance. Many studies have shown the benefit of targeting this cell population by restoring self-tolerance. Therapies that could possibly increase the suppressive ability of T regulatory cells were proven to improve the course of autoimmune diseases.

Background: The suspicion of child abuse and neglect may arise from manifestations such as physical or psychosomatic symptoms, eating disorders, suicidal behavior, impaired parental functioning, etc. Thus the arrival of an abused or neglected child at the hospital provides an opportunity for detecting the problem and beginning a process of change. Optimal utilization of this potential depends on the awareness, diagnostic ability and cooperation of the staff.

Objectives: To assess knowledge about hospital policy, attitudes and actual behavior of hospital staff in cases of SCAN[1].

Methods: The questionnaire was adapted and distributed to a convenience sample of personnel at a children’s hospital. The questionnaire included items on knowledge of hospital policy regarding SCAN, attitudes towards inquiring about cases that appear suspicious, and behaviors in cases in which the respondent was involved. The comparison of responses to specific questions and among members of different professions was analyzed by chi-square test.

Results: Eighty-two staff members completed the questionnaires. Most of the respondents were aware of hospital policy regarding suspected abuse (86.6%), with fewer regarding suspected neglect (77.2%). Physicians were the least aware of these policies, as compared to medical students, nurses and social workers. Although most considered the issue of SCAN a responsibility of members of their own profession, 35.4% considered it primarily the responsibility of the welfare or judicial systems. Over 40% felt uncomfortable discussing suspicions with the child and nearly half felt uncomfortable discussing them with parents. The most often reported reason for this was the sense that they lacked skills or training for dealing with the issue. Despite this, when asked about actual behavior, 94.7% responded that they do try to clarify the circumstances related to the suspicious symptoms. Respondents were more likely to contact the hospital social worker than community resources (91.5% vs. 47.2%).

Conclusions: The findings highlight the need to encourage awareness, discourse and training of medical personnel about issues related to SCAN in order to maximize their potential contribution to identifying children at risk.

Klinefelter's syndrome, which occurs in males, is not a rare gonosomal aberration. The disorder is characterized by micro-orchidism.

Background: In developed countries, the incidence of Sydenham’s chorea, a major sign of rheumatic fever has declined, but outbreaks are still encountered worldwide.

Objectives: To report the characteristics of a cohort of SC[1] patients in the Jerusalem area.

Methods: We conducted a prospective assessment of rheumatic fever and SC between 1985 and 2002. The diagnosis of rheumatic fever was based on the revised Jones criteria. Other etiologies of chorea were excluded. Recurrence was defined as the development of new signs, lasting more than 24 hours and separated by a minimum of 2 months from the previous episode. Patients were followed for 1 to 14 years following the initial SC episode, and at least one year after recurrence.

Results: Among 180 children with rheumatic fever, 24 had SC. Most of them came from large families of Ashkenazi origin. In 19 patients (79%) the chorea was associated with other rheumatic fever signs, while 5 had pure chorea. Due to the systematic use of two-dimensional color Doppler echocardiography, cardiac involvement was detected in 75% of the patients. Ten patients (42%, 7 females) developed 11 recurrent episodes of chorea 3 months to 10 years after the initial episode. At recurrence, chorea was the sole rheumatic sign in all nine patients who recurred once. None of the patients had persistent chorea.

Conclusions: SC is still prevalent in the pediatric population of Jerusalem, and may recur years later. Recognition of the disease and adequate treatment is necessary.

There is accumulating evidence that tumor necrosis factor plays a major role in the pathogenesis of rheumatoid arthritis. Recent biotechnological advances have allowed for the development of agents that directly target TNF, a pro-inflammatory cytokine. In the last 2 years, the U.S. Food and Drug Administration and the European Union’s Commission of the European Communities have approved two biological agents for the treatment of refractory RA, etanercept and infliximab. Etanercept is a fusion protein, composed of the Fc portion of immunoglobulin G1 and the extracellular domain of a TNF receptor (p75). Infliximab is a chimeric monoclonal antibody composed of murine variable and human constant regions. In placebo-controlled trials, both agents have proven to be effective and well tolerated in PA patients.