The human leukocyte antigen (HLA) class II genotype DQA1*0301-DQB1*0302/DQA1*0501-DQB1*0201 has been identified as a marker strongly predisposing to insulin-dependent diabetes mellitus (IDDM) in Caucasian populations. Its frequency in control populations (1-3%) is still, however, 1 order of magnitude higher than the prevalence of IDDM, suggesting that its penetrance can be modified by protective factors. In this study we searched for such a factor in the DRB1 locus by studying DRB1*04 polymorphism in 174 European Caucasian IDDM patients and 73 nondiabetic control subjects, all sharing the HLA-DR3/DR4 phenotype. Significant protection was encoded by the DRB1*0403 allele, which was observed in 5 of 49 control subjects (10%) and none of 171 IDDM patients (0%) with the DQA1*0301-DQB1*0302/DQA1*0501-DQB1*0201 genotype (RR = 0.02 [0.01-0.18], P < 0.0005). These data support the concept that protective HLA class II genes can overrule the risk caused by HLA-DQ susceptibility dimers. They also contribute to a possible strategy to screen for nondiabetic individuals with increased genetic risk of developing IDDM.
We investigated correlations between soluble HLA-DR (sHLA-DR) molecules and several clinical, biological and genetic parameters associated with rheumatoid arthritis (RA) disease activity. Serum sHLA-DR concentrations were determined in 146 samples from 89 RA patients by an ELISA format, using an antibody combination of mouse and rat monoclonal anti-human HLA-DR antibodies. The mean sHLA-DR serum level in RA patients was significantly increased with 277+/-19 ng/ml compared to 142+/-13 ng/ml of 80 healthy controls (P<0.001). In ascending order of significance, correlations were found between serum sHLA-DR and EULAR swelling and pain scores, Waaler-Rose, RA factor, ESR and CRP (P=0.025 to P<0.001). High sHLA-DR levels were defined above 374 ng/ml that was the 95% confidence interval of the controls. Thirty-seven blood samples (25%) in 31 RA patients were above this level. The EULAR pain and swelling scores, erythrocyte sedimentation rate (ESR), C-reactive protein (CRP) and RA factor were higher (P=0.044 to P<0.001) at the moment of high sHLA-DR concentrations, compared to the lower concentrations. Higher disease activity was further found in groups of RA patients respectively heterozygous or homozygous for the disease-associated epitope (Q)R/KRAA within the HLA-DRB1 chain, compared to the group without this epitope (P<0.017 for part of the results). Likewise, sHLA-DR was respectively 169+/-17 (no disease associated epitope), 324+/-34 (heterozygous) and 442+/-69 ng/ml (homozygous for the disease-associated epitope on HLA-DRB1 alleles) (P<0.017). In conclusion, this study shows significant correlations between serum sHLA-DR levels and RA disease activity parameters, as well as increased sHLA-DR in patients with disease-associated epitope on HLA-DRB1 alleles.
The Siberian moth, Dendrolimus sibiricus, Tschtv. is the most harmful defoliator of coniferous forests in North Asia. The pest has already spread over the Urals and continues moving westwards. Recently, it has been recommended for quarantine in member countries by European and Mediterranean Plant Protection Organization (EPPO). The performances of the pest on coniferous species planted in Europe were assessed on a range of potted trees corresponding to the spectrum of economically important conifers in the EU: European larch Larix decidua, Norway spruce Picea abies, Scots pine Pinus sylvestris, European black pine Pinus nigra, and the North American species: Douglas fir Pseudotsuga menziesii and grand fir Abies grandis. Larvae showed a potential to survive and complete the development on all these host tree species. Favorable hosts were grand fir, European larch, and Douglas fir that allowed higher survival, better larval development, and as a result, yielded heavier pupae and adult moths with higher longevity. Black pine was a poor host but, however, could still support larval and pupal development. Norway spruce and Scots pine had an intermediate behavior. If accidentally introduced to Europe, the Siberian moth may become especially damaging in forest stands predominated by European larch and by the North American firs. Norway spruce and especially the two-needle pines will be less prone to intensive defoliation by this species. The fact that the pest may damage the range of economically important coniferous species should be taken into account in the pest risk assessment for Europe and also for North America where the Siberian moth occurrence is considered likely.
The performance of young larvae of the potentially invasive Siberian moth Dendrolimus sibiricus Tschtv. has been studied for the first time on the native and exotic coniferous species which are widely distributed and of considerable commercial value in Europe. Picea, Abies, the introduced Pinus species (five‐needle pine only), and species from the exotic genera Pseudotsuga and Cedrus (all Pinaceae) are found to be suitable hosts for pest development. Two‐needle pines and species from non‐native Tsuga (also Pinaceae) are poor hosts in terms of larval performance though they may support growth of neonates (most sensitive to food quality). Coniferous species from other families: Taxaceae and Cupressaceae are inedible for the pest. The fact that the Siberian moth is able to survive and develop on all the tested genera of Pinaceae and that some of them constitute two thirds of the European forests underline how harmful this defoliator could be in the case of its introduction into European countries.
The effect of pregnancy on the humoral immune response induced by Trypanosoma cruzi was studied in groups of chronically infected and pregnant mice (IP) or chronically infected and nonpregnant mice (INP) of strain BALB/c. Groups of noninfected and nonpregnant mice (NINP) or noninfected and pregnant mice (NIP) served as controls. The pregnant mice were killed on day 17 of pregnancy. Anti-T. cruzi immunoglobulin G (IgG) and IgM antibodies, detected by immunofluorescence or enzyme-linked immunosorbent assay or both, underwent a pregnancy-associated decrease of 20 to 40%, whereas complement-mediated lytic antibodies were unaffected by pregnancy. Immunoblotting analysis indicated identical specificities of the anti-T. cruzi antibodies in IP and INP groups. The levels of all the immunoglobulin isotypes (particularly IgG2a and IgG3), circulating immune complexes, rheumatoid-like factor, and anti-DNA antibodies were considerably increased during chronic infection (NINP versus INP), which could be related to the high degree of polyclonal B-cell activation occurring in T. cruzi infection. However, pregnancy significantly decreased (by 20 to 60%) such parameters. IgG levels were particularly affected (by 40 to 60%), and the decreases could be ordered as follows: IgG3 > IgG2a > IgGI > IgG2b for IP versus INP. Comparisons between the noninfected groups indicated differences only in IgG levels. These results indicate the following. (i) The specific humoral anti-T. cruzi immune response is weakly affected by pregnancy, which is not sufficient to modify the course of the mother's infection. (ii) Pregnancy does not modify the expression of the anti-T. cruzi antibody repertory. (iii) Pregnancy reduces the polyclonal B-cell activation, particularly the levels of the IgG isotypes undergoing the greatest activation.
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