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PubMed2026

Genome-wide association study and KASP development for growth and leaf traits in Populus deltoides.

BACKGROUND: Populus deltoides is a valuable timber species of considerable importance in the study of forest genetic breeding. However, its genetic improvement continues to rely predominantly on conventional selection and hybridization strategies hampered by long breeding cycles and limited efficiency. RESULTS: A total of 209 P. deltoides accessions were genotyped using a 60K SNP (Single nucleotide polymorphism) liquid array. Following quality control, 46,031 high-quality SNPs were screened and analyzed alongside 15 phenotypic traits in a genome-wide association study (GWAS), which identified 219 SNPs significantly associated with the traits. After further screening and annotation, a final set of 57 target SNPs and 77 candidate genes was obtained. Using kompetitive allele-specific PCR (KASP) assays, we successfully developed 48 polymorphic KASP markers. Of these, 25 markers exhibited significant phenotypic differences (p < 0.05) across genotype groups. CONCLUSIONS: These 25 KASP markers can serve as reliable and practical tools for phenotype-assisted selection, providing efficient molecular resources for accelerating genetic improvement and marker-assisted breeding in poplar.

Populus↗

PubMed2026

GWAS-based identification of a candidate gene and development of a predictive KASP marker for seed protein and oil contents in soybean.

BACKGROUND: Soybean [Glycine max (L.) Merrill] is one of the most widely cultivated crops worldwide. Its seeds contain about 40% protein and 20% oil, serving as essential nutrient sources for humans. Given the nutritional importance of seed protein and oil, identifying genes that regulate their levels is crucial for improving soybean seed quality. OBJECTIVE: This study aimed to identify genetic factors associated with seed protein and oil content using a genome-wide association study (GWAS). METHODS: Seed protein and oil contents were quantified in 192 soybean mutant accessions in a mutant diversity pool (MDP), and GWAS was conducted using 17,631 SNPs filtered from genotyping-by-sequencing. Expression of a candidate gene was examined across seed developmental stages (R5 to R7), and a significant SNP was converted into a Kompetitive Allele-Specific PCR (KASP) marker for validation. RESULTS: GWAS detected significant SNPs associated with seed protein and oil content. Chr20_7635098 was identified as a nonsynonymous SNP located in the exon of Glyma.20g042400. This gene showed differential expression across seed developmental stages between mutant accessions with contrasting protein and oil contents. The KASP marker for Chr20_7635098 was validated using the MDP and six domestic soybean cultivars showing predictive accuracies of ≥ 80.50% for protein content and ≥ 61.18% for oil content. CONCLUSION: Overall, this study identified a candidate gene linked to both seed protein and oil content, providing valuable insights for molecular breeding strategies aimed at efficiently improving these nutritional traits.

Glycine max↗

PubMed2026

Development and identification of KASP-SNP markers correlated with Aeromonas hydrophila resistance traits in blunt snout bream (Megalobrama amblycephala).

The blunt snout bream (Megalobrama amblycephala) is an economically important freshwater fish species. However, it is highly susceptible to Aeromonas hydrophila infection, especially in intensive pond aquaculture in China. Molecular marker-assisted selection provides an efficient approach for breeding disease-resistant varieties; however, the key genes or molecular markers linked to A. hydrophila resistance remain scarce in this species. A 436 differential SNP sites with disease-resistant were screened on basis of whole-genome resequencing. Then, a high-throughput genomic KASP genotyping technique was utilized to discover favorable genes and SNP sites associated with A. hydrophila resistance. A total of 46 KASP markers were successfully developed with an accuracy of 92 %. These markers were used to genotyping 120 blunt snout bream individuals. Through trait correlation analysis and general linear models (GLM), five SNPs significantly (P < 0.05) associated with resistance to A. hydrophila were identified and mapped to five candidate genes (btnl2, cfhr2, slc47a1, neu3, nlrp1). Survival rate of individuals carrying the dominant genotype demonstrated an average survival rate of 81.39 %, which represents a 69.35 % increase in comparison with that of 48 % in total population. This effect was validated in an external population of 100 fish. These findings identify key genetic markers associated with A. hydrophila resistance and provide a direction for elucidating the underlying molecular immune mechanisms, thus establishing a genetic foundation for future breeding strategies.

Cyprinidae↗

PubMed2026

A transcriptome-wide approach for rapid pathotype discrimination of Puccinia striiformis f. sp. tritici in north-western India.

Stripe rust of wheat caused by Puccinia striiformis f. sp. tritici (Pst) remains a major constraint to wheat production in India due to the rapid evolution and frequent emergence of virulent pathotypes. Rapid and reliable discrimination of Pst pathotypes is essential for effective resistance deployment and surveillance. In the present study, transcriptome-wide simple sequence repeats (SSRs) and single nucleotide polymorphisms (SNPs) were exploited to develop and validate molecular markers for pathotype-specific detection of Pst pathotypes prevalent in North India (110S119, 238S119, 46S119, 110S84 and 78S84). Microsatellite mining from 6103 core orthologous clusters comprising 51,127 transcripts mined 14,634 SSR loci, from which 93 primer pairs were synthesized. However, only three SSR markers exhibited polymorphism indicating limited discrimination potential of expressed sequence-derived (EST) SSRs for pathotype differentiation. In contrast, SNP discovery through stringent variant calling and filtration yielded 186 pathotype-specific homokaryotic SNPs, of which 56 high-confidence loci were selected for Kompetitive Allele-Specific PCR (KASP) assay development. A total of 48 KASP markers were synthesized and 14 demonstrated clear pathotype- or cluster-specific polymorphism representing substantially higher resolution than SSR markers. The high SNP-to-KASP conversion efficiency (~ 95%) and reproducible fluorescence-based clustering emphasize the robustness of KASP assay. Comparative evaluation revealed that SNP-based KASP markers provide superior discriminatory capacity for closely related Pst pathotypes and represent a promising complementary molecular approach for rapid identification of predominant Indian Pst pathotypes. The validated marker panel developed in this study can complement conventional virulence phenotyping and field pathogenomics approaches for surveillance of currently known pathotypes, while continued refinement may accommodate future changes in pathogen populations.

India↗

PubMed2026

Cloning of two Hsp70 genes and association analysis between SNP haplotypes and high temperature tolerance trait in red swamp crayfish (Procambarus clarkii).

Aquaculture is suffering the challenge from high temperature climate. Two Hsp70 genes, PcHsp70-1 and PcHsp70-2, as key genes involved in the high temperature tolerance of red swamp crayfish (Procambarus clarkii) were identified and cloned in this study. Their molecular features and expression patterns were characterized, revealing the distinct tissue-specific upregulation expression under high temperature stress (33 °C). Two SNPs, PcHsp70-1 (SNP258) and PcHsp70-2 (SNP555) were examined to associate with high temperature tolerance in three populations (n = 675). The genotypes of PcHsp70-1-SNP258 (GA) and PcHsp70-2-SNP555 (TT) were significantly associated with stronger high temperature tolerance. Notably, individuals carrying the haplotype of Hap I (GG + TT) showed a survival rate exceeding 70% under high temperature stress, whereas, the Hap VIII (AA + CT) showed it at 5.2%. RNA interference of PcHsp70-1 resulted in a significant decrease expression of the gene GSH-Px and its encoding protein (glutathione peroxidase) activity, and damage in intestinal tissue under high temperature stress. The transcriptome result revealed that PcHsp70-1 participates in regulation of the pathways related to cytoskeletal construction, immune response, apoptosis, and antioxidant defense. These findings indicate that PcHsp70 genes are crucial for the cellular stress response under high temperature stress. The developed Kompetitive Allele Specific PCR (KASP) markers provide valuable tools for the marker-assisted selection of high temperature tolerant crayfish varieties, supporting the sustainable development of aquaculture under the challenge of global warming.

Animals↗

PubMed2026

Development of molecular markers associated with saline-alkali tolerance in rapeseed (Brassica napus L.).

A total of 947 saline-alkaline tolerance-related molecular markers and a 5K cGPS genotyping chipwere developed, providing practical tools for marker-assisted selection and molecular design breeding of saline-alkaline-tolerant rapeseed. Rapeseed (Brassica napus L.) has relatively strong tolerance to saline-alkaline stress and shows great potential for the sustainable utilization and improvement of saline-alkaline soils. However, the breeding of highly tolerant cultivars still mainly depends on conventional hybridization combined with phenotype-based selection, which constrains breeding efficiency. In this study, previously reported saline-alkaline tolerance-related genes from rapeseed, rice, maize, wheat, sorghum, and Arabidopsis were collected. Candidate gene-based association analysis enabled the development of molecular markers and a genotyping chip. A total of 483 significantly associated genes were identified, among which 355 genes contained favorable haplotypes. Molecular markers were successfully developed for 275 genes, including 746 KASP and 201 InDel marker pairs, and four marker pairs were randomly selected for validation. In addition, a 5K cGPS liquid-phase chip (HZSW-cGPS-BRNAP-04), was developed and showed a high call rate and excellent reproducibility in genotyping. These markers and the chip are expected to improve the breeding efficiency of saline-alkaline-tolerant rapeseed cultivars. Overall, this study provides useful tools for early-generation evaluation and marker-assisted selection (MAS), and provides a foundation for molecular design breeding of saline-alkali-tolerant rapeseed.

Brassica napus↗

PubMed2026

Genome-wide identification of the carotenoid cleavage dioxygenase gene family in wheat and analysis of the TaDREB-7A-TaNCED9a regulatory module conferring drought tolerance.

Carotenoid cleavage dioxygenases (CCDs) play critical roles in plant growth, development, and abiotic stress responses, yet their genome-wide identification and drought response mechanisms remain unexplored in wheat. In this study, 34 TaCCD genes were identified in wheat, distributed across 15 chromosomes and phylogenetically classified into five subfamilies. Gene structure analysis indicated that members within each subfamily shared conserved motifs and similar intron-exon arrangements. Cis-regulatory element analysis suggested the potential roles of these genes in stress adaptation, developmental processes, and hormone signaling. Moreover, prediction of tertiary structures and protein-protein interactions revealed unique structural features and potential interacting partners of the TaCCD proteins. In addition, TaNCED9a, a member of the TaCCD family, showed the highest transcript level in wheat roots among all detected TaCCD genes and was significantly induced by drought stress. Subcellular localization assay indicated that TaNCED9a was located in chloroplasts. Downregulation of TaNCED9a expression led to reduced drought resistance in wheat, accompanied by an accumulation of reactive oxygen species and a decrease in endogenous abscisic acid levels. Using yeast one-hybrid, dual-luciferase, and tobacco transient co-expression assays, the upstream regulatory factor TaDREB-7A was identified, which can regulate the expression of TaNCED9a. Additionally, a KASP molecular marker was developed to identify the superior haplotype TaNCED9a-HapI, which exhibited a significantly higher germination rate compared to TaNCED9a-HapII under drought conditions, and was predominant in wheat. These results offer valuable insights into the TaCCD gene family's response mechanisms to drought stress in wheat, simultaneously identifying promising genetic resources for enhancing drought tolerance through molecular breeding.

CCD↗

PubMed2026

Identification and characterization of PsFwC9 conferring Fusarium wilt resistance in pea.

Pea (Pisum sativum L.) is one of the most important edible legumes in China, with both planting area and total yield ranking among the highest in the world. Fusarium wilt, caused by Fusarium oxysporum f. sp. pisi (Fop), is a severe factor limiting pea production. The deployment of resistant pea cultivars is the most effective and sustainable strategy for controlling this disease. In the present study, a novel resistance gene PsFwC9, conferring resistance to Fop race 5, was identified in the resistant pure line Chengwan 9-8 (CW9-8), and its candidate gene Psat4g213640 was characterized and functionally validated to be associated with disease resistance. Genetic analysis of the F₂ population derived from the cross between the resistant parent CW9-8 and the susceptible parent Chengwan 9-1 (CW9-1) revealed that PsFwC9 was controlled by a single dominant gene. Based on whole-genome resequencing, bulked segregant analysis sequencing (BSA-seq) and fine mapping, PsFwC9 was localized to an 817.06-kb region on chromosome 4 (i.e. linkage group IV, chr4LG4), flanked by KASP markers A016508 and A016511, and co-segregated with four markers. Haplotype analysis revealed that only the marker A016615 was significantly associated with Fusarium wilt resistance, and this marker was designated as a diagnostic marker for PsFwC9. Marker A016615 was located at 425 699 725 bp on chr4LG4, corresponding to the 277 bp within Psat4g213640, where a 'A/G' single-nucleotide polymorphism caused an amino acid substitution leading to an alteration in protein structure; therefore, Psat4g213640 was identified as the PsFwC9 candidate gene. Quantitative real-time PCR analysis showed no significant difference in the expression levels of Psat4g213640 between CW9-8 and CW9-1. Overexpression of the candidate gene Psat4g213640CW9-8 in the hairy root system significantly enhanced the resistance of CW9-1 to Fusarium wilt, whereas RNA interference-mediated silencing of Psat4g213640CW9-8 reduced the resistance of CW9-8, indicating that Psat4g213640CW9-8 played a crucial role in pea resistance to Fusarium wilt. In addition, subcellular localization showed that the protein encoded by Psat4g213640 was targeted to the endoplasmic reticulum. Collectively, these findings not only enriched the gene resources for disease resistance in pea and provided an important foundation for elucidating the molecular mechanism of PsFwC9-mediated resistance, but also provided important technical support for the practical application of molecular breeding for disease resistance in pea.

Journal Article↗

PubMed1991

Marked longevity of human lung parenchymal elastic fibers deduced from prevalence of D-aspartate and nuclear weapons-related radiocarbon.

Normal structure and function of the lung parenchyma depend upon elastic fibers. Amorphous elastin is biochemically stable in vitro, and may provide a metabolically stable structural framework for the lung parenchyma. To test the metabolic stability of elastin in the normal human lung parenchyma, we have (a) estimated the time elapsed since the synthesis of the protein through measurement of aspartic acid racemization and (b) modeled the elastin turnover through measurement of the prevalence of nuclear weapons-related 14C. Elastin purified by a new technique from normal lung parenchyma was hydrolyzed; then the prevalences of D-aspartate and 14C were measured by gas chromatography and accelerator-mass spectrometry, respectively. D-aspartate increased linearly with age; Kasp (1.76 x 10(-3) yr(-1) was similar to that previously found for extraordinarily stable human tissues, indicating that the age of lung parenchymal elastin corresponded with the age of the subject. Radiocarbon prevalence data also were consistent with extraordinary metabolic stability of elastin; the calculated mean carbon residence time in elastin was 74 yr (95% confidence limits, 40-174 yr). These results indicate that airspace enlargement characteristic of "aging lung" is not associated with appreciable new synthesis of lung parenchymal elastin. The present study provides the first tissue-specific evaluation of turnover of an extracellular matrix component in humans and underscores the potential importance of elastin for maintenance of normal lung structure. Most importantly, the present work provides a foundation for strategies to directly evaluate extracellular matrix injury and repair in diseases of lung (especially pulmonary emphysema), vascular tissue, and skin.

Adult↗

PubMed2025

Genetic heterogeneity in patients with enlarged vestibular aqueduct and Pendred syndrome.

BACKGROUND: Pathogenic variants in the SLC26A4 gene, encoding for Cl-/HCO3- and I- anion transporter pendrin, are associated with non-syndromic hearing loss with enlarged vestibular aqueduct (NSEVA) and Pendred syndrome (PDS). In the Caucasian population, up to 75% of patients fail to identify a genetic cause through biallelic mutations in the SLC26A4 gene. The CEVA haplotype could therefore play an important role in the diagnostics of NSEVA. The aim of the study was to determine the genetic etiology of hearing loss with EVA or with fully developed PDS in 37 probands and the functional characterization of novel variants identified in the SLC26A4 gene. METHODS: To determine the genetic etiology, Sanger sequencing, WES and KASP genotyping assay were used. Functional characterization of SLC26A4 variants c.140G>A (p.R47Q), c.415G>A (p.G139R), c.441G>A (p.M147I), c.481T>A (p.F161I), c.1589A>C (p.Y530S) and c.2260del (p.D754Ifs*5) involved determination of iodide influx, total and plasma membrane pendrin expression level and subcellular localization of pendrin by confocal imaging. The nanopore sequencing of nasopharyngeal swab samples was performed to confirm the pathogenic effect of potential splice site variant c.415G>A. RESULTS: Biallelic variants in the SLC26A4 gene (M2 genotype) were identified in ten probands and a complete CEVA haplotype was confirmed in three probands harbouring SLC26A4 monoallelic variants (M1 genotype). Fifteen variants in the SLC26A4 gene were identified in total, three of which are novel. The functional characterization of the novel variants and variants which were not yet functionally characterized confirmed the pathogenic potential of five out of six tested variants (p.G139R, p.M147I, p.Y530S, p.D754Ifs*5, and p.F161I). Analysis of nasopharyngeal swab samples confirmed exon 4 skipping due to novel variant SLC26A4:c.415G>A. Probands with biallelic SLC26A4 variants had significantly larger thyroid volume per m2 of body surface area than subjects with monoallelic SLC26A4 variants and the CEVA haplotype. CONCLUSIONS: The genetic aetiology was determined in 13 out of 37 probands (35%), seven manifested with PDS and six with NSEVA. The present study highlights the importance of functional testing to confirm the pathogenicity of SLC26A4 variants and the phenotype-genotype correlation in SLC26A4-related disorders.

Humans↗

PubMed1988

Differential effect of Bordetella pertussis on experimental posterior uveitis in the black-hooded Lister rat.

The effect of an additional adjuvant, Bordetella pertussis, on the clinical and histopathologic features of experimental autoimmune uveitis in black-hooded Lister rats was investigated. Disease was induced by a single footpad injection of purified retinal S-antigen in Freund's complete adjuvant. In those animals that did not receive B Pertussis the clinical features were those of a retinal vasculitis with disc edema, periphlebitis, and deep retinal infiltrates. In contrast, animals that received B pertussis developed lesions in the pigment epithelium and choroid. Histopathologic studies disclosed focal photoreceptor necrosis associated with mononuclear cell infiltration in both groups of animals. However, in the group that did not receive B pertussis the disease was predominantly a retinitis associated with perivascular infiltration of retinal vessels, whereas in the group that did receive B pertussis the main feature was a focal choroiditis, with superficial retinal lesions being rarely observed. Retinal photoreceptors were the target tissue in both groups of rats, but the route by which they were damaged was altered from predominantly retinal to choroidal by the addition of Bordetella pertussis as an adjuvant. This change may be ascribed to the ability of B pertussis toxin to sensitize vascular endothelium to local mast cell products, these cells being plentiful around choroidal vessels but absent in the retinal circulation.

Adjuvants, Immunologic↗

PubMed1992

Induction of experimental autoimmune uveoretinitis in Lewis rats with purified recombinant human retinal S-antigen fusion protein.

Full-length human retinal cDNA for S antigen (S-ag) and for the alpha subunit of transducin (alpha-Td) were subcloned into a bacterial expression plasmid vector to generate recombinant fusion proteins with glutathione-S-transferase (GST). The recombinant GST-S-ag and rGST-alpha-Td fusion proteins were purified from bacterial extracts by continuous flow preparative gel electrophoresis under denaturing conditions, and were assessed for their ability to induce experimental autoimmune uveoretinitis (EAU). Immunization of Lewis rats with single doses of 10 micrograms-100 micrograms rGST-S-ag in Freund's complete adjuvant supplemented with Bordetella pertussis readily induced clinical signs of EAU. Immunization with GST alone did not induce EAU indicating that disease activity was ascribable to the S-ag residues in the fusion protein. Although the alpha-Td shares limited sequence homology with S-ag, the rGST-alpha-Td fusion protein was also not uveitogenic in Lewis rats. The clinical severity of EAU in Lewis rats sensitized with rGST-S-ag was found to be milder than that induced with native S-ag preparations purified from human retina. However, humoral antibody responses to sensitization with the recombinant S-ag fusion protein were of a higher magnitude than with native S-ag. The availability of recombinant preparations of human S-ag protein will be of value in studying its processing and presentation to T cells derived from patients with autoimmune retinal vasculitis.

Animals↗

PubMed1987

An improved method for the purification of retinal S-antigen using selective hydrophobic adsorption chromatography.

This paper describes the use of phenyl-Sepharose CL-4B as a solid-phase hydrophobic adsorbent in the purification of S-antigen from protein extracts of bovine, porcine and human retina. Chromatographic conditions were ascertained whereby the majority of contaminating proteins were bound to the adsorbent leaving S-antigen in the liquid phase. In combination with size fractionation on Ultrogel AcA, the method conveniently yielded porcine and bovine S-antigen preparations up to 100% purity. Immunogenicity of purified S-antigens was verified by induction of experimental autoimmune uveoretinitis in albino Lewis rats. The method is preparative in scale, fast in performance and yields S-antigen in high purity and antigenic potency.

Adsorption↗

PubMed1992

Antibody affinity to retinal S-antigen in patients with retinal vasculitis.

Using a modified enzyme-linked immunosorbent antibody method that included dissociation of antigen antibody complexes with sodium thiocyanate, we examined the functional affinity of antibody to retinal S-antigen in 48 patients with retinal vasculitis and 46 age-matched healthy control subjects. Antibody affinity was markedly lower in patients with retinal vasculitis than in healthy subjects. Low-affinity antibody was more prevalent in acute retinal vasculitis and in patients with normal levels of circulating immune complexes. We found distinct differences between the antiretinal antibodies found in patients with retinal vasculitis and those in control subjects. The association of low-affinity antibody with normal levels of circulating immune complexes may suggest defective regulation of antiretinal autoimmunity and have important pathogenic implications.

Antibody Affinity↗

PubMed1987

Comparative biochemical analysis of purified S-antigen from human, bovine, porcine and rat retina.

Highly purified S-antigen from human, bovine, porcine and rat retina was used to ascertain the molecular weights, isoelectric points, amino-acid composition and presence of carbohydrate moieties. All S-antigen preparations comigrate to 50,000 MW on SDS-polyacrylamide gels and demonstrate microheterogeneity upon isoelectric focusing. Human S-antigen exhibits two bands at pH 5.9 and 5.6, whilst with bovine S-antigen a broad band at pH 5.9 was observed. Porcine and rat S-antigen gave four bands, focusing between pH 5.0-5.6. Two-dimensional gel analysis revealed that all the four focused porcine polypeptides migrate to 50,000 MW. Western-blot analysis following isoelectric focusing of human and porcine S-antigen showed that all polypeptide bands react specifically with polyclonal and monoclonal antibodies to S-antigen. The reasons for the apparent heterogeneity of S-antigen by isoelectric focusing are discussed. All S-antigen preparations were weakly positive for periodic acid Schiff staining, and specifically bound radiolabelled Lens culinaris lectin on Western-blot analysis. These results confirm the glycoprotein nature of S-antigen which may explain the finding of multiple bands found on isoelectric focusing. Amino-acid analysis reveals the high percentage of non-polar amino acids and may explain the apparent hydrophobic behaviour of the isolated protein.

Amino Acids↗

PubMed1987

Retinal vasculitis: correlation of animal and human disease.

A form of experimental retinal vasculitis was induced in black hooded Lister rats by the inoculation of retinal S-antigen. Comparison of this disease with retinal vasculitis in man showed striking clinical, angiographic and pathological similarities. Clinically disc oedema, periphlebitis and retinal infiltrates were observed with corresponding leakage of dye on fluorescein angiography. Pathologically the disease showed perivascular lymphocytic infiltrates with focal photoreceptor necrosis. These characteristic features make this an ideal model for the study of the pathogenesis of retinal vasculitis in man.

Animals↗

PubMed1987

Modulation of experimental retinal vasculitis using dexamethasone, cyclosporin A, and prazosin.

The effects of dexamethasone, cyclosporin A and prazosin were investigated in an animal model of retinal vasculitis. Both dexamethasone and cyclosporin A reduced the clinical and pathological signs of disease when given from the day of disease onset. Prazosin, an alpha 1 adrenergic antagonist, was given during the period of disease induction and blocked fluorescein leakage from actively inflamed retinal vessels, but had little effect on the clinical and pathological signs of disease. This study demonstrates the feasibility of using this animal model for therapeutic trials of anti-inflammatory agents in retinal vasculitis. The effect of prazosin on reducing vascular leakage from retinal vessels has implications for the treatment of inflammatory macula oedema in human disease.

Animals↗

PubMed1992

Circulating immune complexes may play a regulatory and pathogenic role in experimental autoimmune uveoretinitis.

We compared the time course of changes in serum levels of circulating immune complexes (CICs) and of IgG antibody after sensitization of albino Lewis and pigmented Lister strain rats with uveitogenic (retinal S-antigen) and non-uveitogenic (ovalbumin) protein antigens of comparable molecular weight. Normal levels of CICs were far lower in Lewis rats in which experimental autoimmune uveoretinitis (EAU) takes the form of a severe panuveitis, than in Lister rats, in which the disease is mild, focal, confined to the posterior segment, and of lower incidence. After sensitization with either S-antigen or ovalbumin, polyethylene-glycol-precipitable CIC (PEG-CIC) peaked and fell as IgG antibody levels rose in both rat strains. However, peak levels of PEG-CIC were lower and subsequent IgG antibody levels were higher in the Lewis strain than in the less susceptible Lister strain. In both strains of rat these linked PEG-CIC/IgG antibody responses occurred earlier after sensitization with uveitogenic (S-) antigen than with ovalbumin, whether or not individual S-antigen-sensitized Lister rats developed EAU. In contrast, complement-binding CIC rose substantially only in those rats of both strains displaying EAU in response to S-antigen and not in response to ovalbumin. We suggest that immune complex (idiotypic) regulation of IgG antibody responses may be more readily perturbed by a pathogenic autoantigen (S-antigen) than by a bland antigen (ovalbumin). We also suggest that differences between the balance of regulatory and pathogenic CIC responses to uveitogenic retinal antigen may underlie or reflect strain differences in susceptibility to and severity of EAU.

Animals↗