What can we learn from genetic studies of systemic lupus erythematosus? Implications of genetic heterogeneity among populations in SLE

Lupus ◽  
2010 ◽  
Vol 19 (12) ◽  
pp. 1452-1459 ◽  
Author(s):  
H-S. Lee ◽  
S-C. Bae
Keyword(s):  
Immune Response ◽  
Allele Frequency ◽  
Genetic Heterogeneity ◽  
Lupus Erythematosus ◽  
Genetic Factors ◽  
Risk Allele ◽  
Adaptive Immune Response ◽  
Environment Interaction ◽  
Risk Allele Frequency ◽  
Hla Dr

Recent progress in genetics has expanded the number of the genes associated with SLE to more than 20 in the past 2 years. One might assign these candidate genetic factors into several pre-existing biological pathways: (i) innate immune response including TLR/interferon signaling pathways (IRF5, STAT4, TNFAIP3, and TREX1); (ii) adaptive immune response (HLA-DR, PTPN22, PDCD1, STAT4, LYN, BLK, and BANK1) including B, T cells, and antigen-presenting cells; and (iii) immune complex clearance mechanism (FCGRs, CRP, and ITGAM). In addition, there are also several genes and loci that could not be assigned into previous known pathways (KIAA1542, PXK, XKR6, ATG5, etc), providing possible novel mechanisms in SLE. It has also been evident that there are similarities and differences in SLE susceptibility loci across ethnic groups. Here we categorize the susceptible genes into four groups. The first group is the consistently associated genes with similar risk allele frequency between multiple ethnic populations such as STAT4, TNFAIP3, BANK1, and IRAK1/MECP2. The second group is the genes that are consistently associated but show marked difference in risk allele frequency (BLK, IRF5). The third group is the genes in which different risk variants exist within a gene or genetic loci (allelic heterogeneity) such as HLA-DR, FCGRs, and IRF5. The fourth group is the genes that show consistently discrepancy between populations such as PTPN22 and possibly ITGAM, PXK, and LYN (genetic heterogeneity). The possible explanations for differences of susceptible genetic factors between populations could be different genetic backgrounds, contribution of gene—gene or gene—environment interaction, and the relation between marker and causal variants. Therefore, efforts to identify ethnic-specific genetic factors or disease causing variants should be necessary for individualized therapy for SLE in future.

scholarly journals Formation of Cellular Responses in the Adaptive Immune Response of 40–60-Year-Old Women Living in Northern Russia

2020 ◽  
pp. 350-359
Author(s):  
Mohammad S. Kabbani ◽  
◽  
Oksana E. Filippova ◽  
Elizaveta Yu. Shashkova ◽  
Marina V. Men’shikova ◽  
...  
Keyword(s):  
Immune Response ◽  
Major Histocompatibility Complex ◽  
Major Histocompatibility Complex Class ◽  
Adaptive Immune Response ◽  
Class Ii ◽  
Natural Killers ◽  
Complex Class ◽  
Adaptive Immune ◽  
Histocompatibility Complex ◽  
Hla Dr

Sustainable development of Russian Arctic territories requires creating favourable living conditions and preserving public health. Living in high latitudes, one is exposed to adverse environmental factors, which can lead to changes in the activity of life functions, including the immune response. The study of the lymphoid population ratio allows us to reveal the age-related formation of the adaptive immune response in women born and living in the Russian North, which is especially important given the increasing retirement age. The purpose of this work was to determine the ratio of lymphoid populations in the adaptive immune response in women between the ages of 40 and 60 born and living in the North of the Russian Federation. Two groups of women – aged 40–49 and 50–60 years – living in the town of Nadym (Yamalo-Nenets Autonomous Okrug) and Pinega settlement (Arkhangelsk Region) were examined using the method of indirect immunoperoxidase reaction with monoclonal antibodies (Sorbent, Moscow). The analysis on the immune status included determining lymphocytes with CD3+ (mature lymphoid cells), CD4+ (T helper cells), CD8+ (cytotoxic T lymphocytes), CD16+ (natural killers), and HLA-DR+ (activated В cells with major histocompatibility complex class II receptors) markers in the peripheral blood. We found that the adaptive immune response is formed in 40–49-year-old women as a result of cell-mediated cytotoxic activity of the T-cell component (CD8+) in 68.0 % and due to natural killers (CD16+) in 72.0 % of cases; in women aged 50–60 years, as a result of a pronounced deficiency of mature and functionally active T cells (CD3+) in 96.3 %, low helper activity (CD4+) in 18.5 %, and decreased activation of lymphocytes with major histocompatibility complex class II receptors (HLA-DR+) reflecting B-cell activity in 25.9 % of cases.

Role of non-resident subpopulations of mucosal and adaptive immune systems in patients with chronic periodontitis

2021 ◽  
Vol 1 (30) ◽  
pp. 61-66
Author(s):  
V. P. Mudrov ◽  
N. V. Davidova ◽  
S. P. Kazakov ◽  
T. E. Mishina
Keyword(s):  
Immune Response ◽  
Immune System ◽  
Chronic Periodontitis ◽  
Periodontal Diseases ◽  
Single Cells ◽  
Adaptive Immune Response ◽  
Adaptive Immune System ◽  
Quantitative Composition ◽  
Adaptive Immune ◽  
Hla Dr

Periodontal bacterial bioflm causes an innate and adaptive immune response of the host mucosa, leading to inflammation and destruction of the tissues supporting the periodontal. The progression of periodontitis depends not only on bacteria, since an inadequate immune response to microorganisms can accelerate the development of periodontitis. However, the exact mechanisms of the development of immune reactions remain unclear. Recent studies emphasize the existence of a typical innate response of resident and extravasated immune cells.Objective. To investigate the quantitative composition of non-resident subpopulations of lymphocytes in salivary fluid and to study the mechanisms of interaction of the cellular link of the innate and adaptive immune system in chronic generalized periodontitis of varying severity.Materials and methods. 49 people aged 26–67 years of both sexes were examined with a diagnosis of chronic periodontitis. The comparison group consisted of 17 people aged 26–44 years with no periodontal diseases. The state of the cellular link of the adaptive and local immune system of the oral cavity was assessed by the following phenotypes: CD3–CD16+56+; CD3+CD16+56+; CD3+; CD3+HLA-DR+; CD19+, CD19+HLA-DR+; CD19+CD5+CD27–; CD19+CD5–СD 27–; CD19+СD5–CD27+.Results. The number of T-NK cells decreased with a mild degree of periodontitis and increased with a severe degree. Similarly, CD3+HLA-DR+ decreased with mild periodontitis [Me = 0.148 cells/µl] and increased with moderate [Me = 0.247 cells/µl] and severe [Me = 0.448 cells/µl]. The number of B-lymphocytes with the CD19+, CD19+CD5+, CD19+CD5–CD27+ phenotype decreased to single cells per microliter during the development of the disease.Conclusion. The imbalance of the immune system caused by pathogenic colonization of the periodontium, at different degrees of severity, is an important factor in the occurrence and development of periodontitis, in which various subsets of B cells of the adaptive immune system play a certain role, closely interacting with the cellular link of the innate mucosal immune system

A systematic review of the Trypanosoma cruzi genetic heterogeneity, host immune response and genetic factors as plausible drivers of chronic chagasic cardiomyopathy

Parasitology ◽  
2018 ◽  
Vol 146 (3) ◽  
pp. 269-283 ◽  
Author(s):  
Paula Jiménez ◽  
Jesús Jaimes ◽  
Cristina Poveda ◽  
Juan David Ramírez
Keyword(s):  
Systematic Review ◽  
Immune Response ◽  
Trypanosoma Cruzi ◽  
Virulence Factors ◽  
Genetic Heterogeneity ◽  
Genetic Factors ◽  
International Consensus ◽  
Host Genetic ◽  
Chagasic Cardiomyopathy ◽  
Host Genetic Factors

AbstractChagas disease is a complex tropical pathology caused by the kinetoplastid Trypanosoma cruzi. This parasite displays massive genetic diversity and has been classified by international consensus in at least six Discrete Typing Units (DTUs) that are broadly distributed in the American continent. The main clinical manifestation of the disease is the chronic chagasic cardiomyopathy (CCC) that is lethal in the infected individuals. However, one intriguing feature is that only 30–40% of the infected individuals will develop CCC. Some authors have suggested that the immune response, host genetic factors, virulence factors and even the massive genetic heterogeneity of T. cruzi are responsible of this clinical pattern. To date, no conclusive data support the reason why a few percentages of the infected individuals will develop CCC. Therefore, we decided to conduct a systematic review analysing the host genetic factors, immune response, cytokine production, virulence factors and the plausible association of the parasite DTUs and CCC. The epidemiological and clinical implications are herein discussed.

scholarly journals HLA-DPB1*03 as Risk Allele and HLA-DPB1*04 as Protective Allele for Both Early- and Adult-Onset Multiple Sclerosis in a Hellenic Cohort

2020 ◽  
Vol 10 (6) ◽  
pp. 374 ◽  
Author(s):  
Maria Anagnostouli ◽  
Artemios Artemiadis ◽  
Maria Gontika ◽  
Charalampos Skarlis ◽  
Nikolaos Markoglou ◽  
...  
Keyword(s):  
Multiple Sclerosis ◽  
Allele Frequency ◽  
Risk Allele ◽  
Laboratory Data ◽  
Protective Role ◽  
Adult Onset ◽  
Protective Allele ◽  
Hla Dr ◽  
Hla Dq

Background: Human Leucocyte Antigens (HLA) represent the genetic loci most strongly linked to Multiple Sclerosis (MS). Apart from HLA-DR and HLA–DQ, HLA-DP alleles have been previously studied regarding their role in MS pathogenesis, but to a much lesser extent. Our objective was to investigate the risk/resistance influence of HLA-DPB1 alleles in Hellenic patients with early- and adult-onset MS (EOMS/AOMS), and possible associations with the HLA-DRB1*15:01 risk allele. Methods: One hundred MS-patients (28 EOMS, 72 AOMS) fulfilling the McDonald-2010 criteria were enrolled. HLA genotyping was performed with standard low-resolution Sequence-Specific Oligonucleotide techniques. Demographics, clinical and laboratory data were statistically processed using well-defined parametric and nonparametric methods and the SPSSv22.0 software. Results: No significant HLA-DPB1 differences were found between EOMS and AOMS patients for 23 distinct HLA-DPB1 and 12 HLA-DRB1 alleles. The HLA-DPB1*03 allele frequency was found to be significantly increased, and the HLA-DPB1*02 allele frequency significantly decreased, in AOMS patients compared to controls. The HLA-DPB1*04 allele was to be found significantly decreased in AOMS and EOMS patients compared to controls. Conclusions: Our study supports the previously reported risk susceptibility role of the HLA-DPB1*03 allele in AOMS among Caucasians. Additionally, we report for the first time a protective role of the HLA-DPB1*04 allele among Hellenic patients with both EOMS and AOMS.

scholarly journals Risk assessment of FLT3 and PAX5 variants in B-acute lymphoblastic leukemia: a case–control study in a Pakistani cohort

PeerJ ◽  
2019 ◽  
Vol 7 ◽  
pp. e7195 ◽  
Author(s):  
Ammara Khalid ◽  
Sara Aslam ◽  
Mehboob Ahmed ◽  
Shahida Hasnain ◽  
Aimen Aslam
Keyword(s):  
Risk Assessment ◽  
Acute Lymphoblastic Leukemia ◽  
B Cell ◽  
Allele Frequency ◽  
Risk Allele ◽  
Lymphoblastic Leukemia ◽  
Genotype Frequency ◽  
Risk Allele Frequency ◽  
Link Type ◽  
Cell Acute Lymphoblastic Leukemia

AIMS B-cell acute lymphoblastic leukemia (B-ALL) is amongst the most prevalent cancers of children in Pakistan. Genetic variations in FLT3 are associated with auto-phosphorylation of kinase domain that leads to increased proliferation of blast cells. Paired box family of transcription factor (PAX5) plays a critical role in commitment and differentiation of B-cells. Variations in PAX5 are associated with the risk of B-ALL. We aimed to analyze the association of FLT3 and PAX5 polymorphisms with B cell leukemia in Pakistani cohort. METHODS We collected 155 B-ALL subject and 155 control blood samples. For analysis, genotyping was done by tetra ARMS-PCR. SPSS was used to check the association of demographic factors of SNPs present in the population with the risk of B-ALL. RESULTS Risk allele frequency A at locus 13q12.2 (rs35958982, FLT3) was conspicuous and showed positive association (OR = 2.30, CI [1.20–4.50], P = 0.005) but genotype frequency (OR = 3.67, CI [0.75–18.10], P = 0.088) failed to show any association with the disease. At locus 9p13.2 (rs3780135, PAX5), the risk allele frequency was significantly higher in B-ALL subjects than ancestral allele frequency (OR = 2.17, CI [1.37–3.43], P = 0.000). Genotype frequency analysis of rs3780135 polymorphism exhibited the protective effect (OR = 0.55, CI [0.72–1.83], P = 0.029). At locus 13q12.2 (rs12430881, FLT3), the minor allele frequency G (OR = 1.15, CI [1.37–3.43], P = 0.043) and genotype frequency (OR = 2.52, P = 0.006) reached significance as showed p < 0.05. CONCLUSION In the present study, a strong risk of B-cell acute lymphoblastic leukemia was associated with rs35958982 and rs12430881 polymorphisms. However, rs3780135 polymorphism showed the protective effect. Additionally, other demographic factors like family history, smoking and consanguinity were also found to be important in risk assessment. We anticipate that the information from genetic variations in this study can aid in therapeutic approach in the future.

scholarly journals Evaluation of Selected Parameters of the Specific Immune Response against Pseudomonas aeruginosa Strains

Cells ◽  
2021 ◽  
Vol 11 (1) ◽  
pp. 3
Author(s):  
Michał Dzik ◽  
David Aebisher ◽  
Alina Olender ◽  
Jacek Tabarkiewicz
Keyword(s):  
Immune Response ◽  
Pseudomonas Aeruginosa ◽  
Immune Responses ◽  
Adaptive Immune Response ◽  
Systemic Infection ◽  
Specific Immune Response ◽  
Opportunistic Pathogens ◽  
Adaptive Immune ◽  
Th17 Lymphocytes ◽  
Hla Dr

The immune response to Pseudomonas aeruginosa strains could be influenced by differences in antibiotic resistance and virulence. At the present time, it is unclear which type of immune responses enables uncontrolled invasion of opportunistic pathogens. The conditional pathogenicity of Pseudomonas aeruginosa served as an inspiration to begin a study on this bacterium. The aim of this study was to gain insight into selected parameters describing immune responses with regards to the adaptable agents of this pathogen. For the analysis of the specific immune response, the potential of Pseudomonas aeruginosa to stimulate lymphocytes, including Th17 lymphocytes, dendritic cells and other components of the adaptive immune response, was examined. The highest percentage of CD83+CD1a-HLA-DR++ cells was found after stimulation with lysates of strains isolated from the patients with severe systemic infection. We found statistically significant differences in percentages of HLA-DR+ PBMCs and MFI of HLA-DR between groups of Pseudomonas aeruginosa strains isolated from the patients with different clinical courses of infection. Our results suggest that the clinical course and outcomes of Pseudomonas aeruginosa infections are not associated with impairment of the specific immune response.

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