Cross-reactive idiotopes among anti-foot and mouth disease virus neutralizing antibodies.

Foot and mouth disease virus (FMDV) viral protein 1 is the only one of the four viral proteins (VP) that induces neutralizing antibodies as an isolated protein. A 32 amino acid (AA) residue (32dimer) of FMDV subtype A12 Lp ab VP1 (AA 137-168) was immunogenic against the A12 subtype. Three antibody populations each recognizing different epitopes on 32dimer were isolated by affinity chromatography (AFC) from the serum of a steer which had been immunized with the 32dimer. The 32dimer contains an AA sequence that is recognized by a protective paratope carried on a murine monoclonal antibody (mAb) (7SF-3.H3.1). Polyclonal anti-7SF-3 idiotype antibodies specifically inhibited the binding activity of one of these anti-32dimer antibody populations suggesting the existence of cross-reactive paratopic-related idiotopes between mAb 7SF-3 and antibodies elicited by the 32dimer. These anti-idiotypic antibodies were used in AFC to purify antibodies from the anti-32dimer serum. The purified antibody population has characteristics that resemble those of the mAb 7SF-3, i.e. its reactivity with FMDV A subtypes in ELISA, radioimmunoassay (RIA), mouse neutralization and its lack of reactivity with a mAb 7SF-3 neutralizing escape virus variant. Furthermore, these antibodies were specifically inhibited by either anti-mAb 7SF-3 idiotypic antibodies or peptides containing the mAb 7SF-3 epitope. Using the same experimental approach, mAb 7SF-3 idiotope-bearing antibodies were shown to be present in serum from bovine and swine convalescent from FMDV A12 Lp ab infection. Thus, the highly immunogenic area between residues 137 and 168 of FMDV VP1 elicited a cross-reactive neutralizing idiotope response conserved amongst several animal species.     

Characterization of anti-idiotypic antibodies generated against foot-and-mouth disease virus neutralizing monoclonal antibodies

A series of seven neutralizing monoclonal antibodies (nMAbs) against type A12 foot-and-mouth disease virus (FMDV) was used to induce polyclonal anti-idiotypic antibodies (anti-ids) in rabbits. The anti-ids were semi-purified through isotype affinity columns and assayed by solid-phase radioimmunoassay for cross-reactivity. nMAbs which map to the same epitope on the virion appear to contain a common idiotype, and the corresponding anti-ids competitively inhibited the virus-nMAb reaction. Using a modified ELISA assay, it was possible to demonstrate binding of purified anti-ids to FMDV susceptible tissue culture cells. Such antibodies however, did not interfere with the binding of virus to cells, and the binding of anti-ids to FMDV receptor-negative cells could also be demonstrated. Mice were inoculated with purified anti-ids, and two elicited anti-viral antibodies, although these antibodies were non-neutralizing. Thus anti-ids to anti-FMDV nMAbs failed to react with cellular receptors for the virus, but were able to induce anti-viral antibody and thus should be examined as an alternative vaccine strategy for this virus.     

Pulmonary hypertension in systemic lupus erythematosus: prevalence,predictors and diagnostic strategy

ObjectivesTo investigate the prevalence and predictors of pulmonary hypertension (PH) in patients with systemic lupus erythematosus (SLE) and to validate a diagnostic strategy.Methods245 patients with SLE entered a screening program. Possible PH was defined as two consecutive systolic pulmonary arterial pressure (PAP) values ≥ 40 mm Hg by echocardiography. The subsequent diagnostic procedure, including right heart catheterization if needed, confirmed or excluded the diagnosis of PH secondary to cardiopulmonary disease or SLE-related pulmonary arterial hypertension (PAH). Independent predictors of PH were identified by multivariant multiple linear or logistic regression models. The sensitivity (S), specificity (SP), positive (PPV) and negative predictive values (NPV) were calculated for different screening cutoff values.Results88% patients were women. The mean (SD) age at the time of enrolment was 45 (16) years. 12 cases of PH were detected, all secondary, with a resulting prevalence of 5%. Two consecutive echocardiographic PAP measurements ≥ 40 mm Hg performed best as the cutoff point for screening (S 100%, SP 97%, PPV 70, NPV 100), as compared with single PAP measurements ≥ 30 mm Hg or ≥ 40 mm Hg The age at the time of enrolment was the only variable independently associated with PAP values (p = 0.0001), with the SLICC damage index score showing a borderline association (p = 0.08). Only the age at the time of enrolment showed an independent association with PH (OR 1.10, 95% CI 1.06–1.17).ConclusionWe found a low prevalence of PH. Screening echocardiograms in asymptomatic lupus patients are thus not recommended. Two consecutive PAP values ≥ 40 mm Hg by echocardiogram is the best screening cutoff for starting investigations in SLE patients with suspected PH.     

Malignant melanoma mortality rates in Chile (1988-98)

BACKGROUND: Malignant melanoma (MM) mortality has increased in the Caucasian population many fold over the past several decades. In this study, we analyzed the Chilean-specific, age-adjusted MM mortality rates per 100,000 population during the decade 1988-98 in order to establish changes in that period. METHODS: We analyzed all death certificates from the Chilean Death Registry Office (1988-98) and retrieved the deaths attributed to MM. The data were categorized according to sex and age group. The annual age-adjusted and sex-specific rates of MM mortality per 100,000 population were calculated. RESULTS: Chilean MM mortality rates increased by 14% between 1988 and 1998. The relative risk for males vs. females was 1.3 with a tendency to rise, showing an increase of 30%. The relative risk of dying from MM in Chile increased linearly with age. An individual of 75 years or older had a 44.24 times greater risk of dying of MM than an individual in the 0-44-year age group. The rates in the > 75-year age group also showed a tendency to rise over the decade, with an increase of 64% (1988-98). CONCLUSIONS: The Chilean MM mortality rates are lower than the world standardized rates. The total Chilean MM mortality rates showed an increase over the decade 1988-98, mainly due to MM mortality in males. The MM mortality in Chilean females was lower than that in males, and was unchanged over the decade; this is in agreement with the results reported in other countries. This is one of the first studies of MM mortality in the Chilean population. The results are important when the geographic location of Chile is considered.