The influence of HLA/HIV genetics on the occurrence of elite controllers and a need for therapeutics geotargeting view

The interaction of HIV-1, human leukocyte antigen (HLA), and elite controllers (EC) compose a still intricate triad. Elite controllers maintain a very low viral load and a normal CD4 count, even without antiretrovirals. There is a lot of diversity in HIV subtypes and HLA alleles. The most common subtype in each country varies depending on its localization and epidemiological history. As we know EC appears to maintain an effective CD8 response against HIV. In this phenomenon, some alleles of HLAs are associated with a slow progression of HIV infection, others with a rapid progression. This relationship also depends on the virus subtype. Epitopes of Gag protein-restricted by HLA-B*57 generated a considerable immune response in EC. However, some mutations allow HIV to escape the CD8 response, while others do not. HLA protective alleles, like HLA-B*27, HLA-B*57 and HLA-B*58:01, that are common in Caucasians infected with HIV-1 Clade B, do not show the same protection in sub-Saharan Africans infected by HIV-1 Clade C. Endogenous pathway of antigen processing and presentation is used to present intracellular synthesized cellular peptides as well as viral protein fragments via the MHC class I molecule to the cytotoxic T-lymphocytes (CTLs). Some epitopes are immunodominant, which means that they drive the immune reaction to some virus. Mutation on an anchor residue of epitope necessary for binding on MHC class I is used by HIV to escape the immune system. Mutations inside or flanking an epitope may lead to T cell lack of recognition and CTL escape. Studying how immunodominance at epitopes drives the EC in a geographically dependent way with genetics and immunological elements orchestrating it may help future research on vaccines or immunotherapy for HIV. 2021 Sociedade Brasileira de Infectologia. Published by Elsevier España, S.L.U. This is an open access article under the CC BY-NC-ND license

Troponin I (cTnI) fragments immunoreactivity and the development of high-sensitivity diagnostic assays for the associated diagnosis of acute myocardial infarction / Imunorreatividade de fragmentos da troponina I (cTnI) e desenvolvimento de ensaios de alta sensibilidade para o diagnóstico associado do infarto agudo do miocárdio

ABSTRACT Among the cardiovascular diseases (CVD), acute myocardial infarction (AMI) is currently considered the most common cause of death and disability worldwide. Several laboratory tests have been developed for the detection of cardiac injury, including troponins that are considered the gold standard marker (surrogate biomarker) of myocardial injury. The high specificity of troponin for cardiomyocyte necrosis is related to a single unique peptide sequence present in troponin at the cardiac muscle. As a result, studies are currently focused on the development of troponin (hs-cTnI) determination tests with high diagnostic sensitivity value. These diagnostic tests aim to detect increasingly lower serum concentrations of cTnI biomarkers, from the detection of peptide fragments that are released after structural biochemical changes. This article discusses the differences between troponin fragments immunoreactivity to the development of cTnI determination tests, such as the high-sensitivity tests, which arise with the proposal of guaranteeing greater efficiency in the AMI associated diagnosis.

RESUMO Entre as doenças cardiovasculares (DCV), o infarto agudo do miocárdio (IAM) atualmente é considerado a causa mais comum de morte e incapacidade em todo o mundo. Vários testes laboratoriais vêm sendo desenvolvidos para a detecção de lesões cardíacas, entre eles, as troponinas, consideradas marcador (biomarcador sugestivo) padrão-ouro de lesão miocárdica. A alta especificidade da troponina para a necrose dos cardiomiócitos está relacionada com a sequência peptídica única presente na troponina do músculo cardíaco. Em função disso, estudos estão voltados para o desenvolvimento de conjuntos diagnósticos de alta sensibilidade para a determinação das troponinas I (hs-cTnI). Esses conjuntos diagnósticos surgem com o objetivo de detectar concentrações séricas cada vez menores desses biomarcadores a partir da detecção de fragmentos peptídicos que são liberados após modificações bioquímicas estruturais. O presente artigo discorre sobre as diferenças de imunorreatividade dos fragmentos de troponina no desenvolvimento de nossos testes para a determinação da cTnI, a exemplo dos testes de alta sensibilidade, que surgem com a proposta de garantir maior eficiência no diagnóstico associado do IAM.

Optimization of immunodominant protein combinations for serological screening for Chlamydia trachomatis infection / 中华皮肤科杂志

Objective To optimize immunodominant protein combinations for serological screening for Cblamydia trachomatis (Ct) infection.Methods Both serum and genital swab samples were collected from 50 patients with Ct infection confirmed by colloidal gold immunochromatographic assay (GICA),and 30 GICA-negative clients without Ct infection at a sexually transmitted disease (STD) clinic in Tianjin Medical University General Hospital.The 30 serum samples from GICA-negative clients were also negative for microimmunofluorescence (MIF) assay.Eight Ct immunodominant proteins,including Pgp3,CPAF,CT143,CT101,CT694,CT875,CT813 and IncA,were selected as antigens to detect corresponding antibodies in the serum samples by enzyme-linked immunosorbent assay (ELISA) with the Ct proteins Hsp60 and major outer membrane protein (MOMP) as references.The results of ELISA were compared with those of the traditional gold standard method MIF assay to determine the immunodominant protein combination with the highest sensitivity and specificity.Results Of the 50 serum samples from patients with Ct infection,44 were positive and 6 negative by MIF.The results of ELISA with the combination of immunodominant proteins Pgp3,CT694 and CT875 as antigens were 97.73％ (43/44) consistent to those of MIF assay.Of the 30 serum samples from GICA-negative clients,all were negative by MIF.Meanwhile,no antibody was detected against any of the immunodominant proteins Pgp3,CT694 and CT875 in any of the serum samples from GICA-negative clients.Conclusions The ELISA with the combination of immunodominant proteins Pgp3,CT694 and CT875 as antigens has good sensitivity and specificity for serological screening for Ct infection,and is simple to operate and easy to popularize.

Impact of human leukocyte antigen-B specific Bw4 epitope on hepatitis C virus infection / 中华传染病杂志

Objective To study the impact of human leukocyte antigen (HLA)-B specific Bw4 epitope on disease progression of hepatitis C virus (HCV) infection.Methods Eighty-six cases of HCV infection through paid blood donation were enrolled in the study.Enzyme-linked immunosorbent assay (ELISA) to detect HCV IgG and IgM,real-time reverse transcriptation polymerase chain reaction (RT-PCR) to detect HCV RNA,and sequence specific primer-polymerase chain reaction (SSP-PCR) to analyze HLA type was performed.Categorical data were analyzed by chi-square test,and measurement data were compared by independent sample t test.Results Among the 86 HCVinfected individuals,there were 29 (33.7 ％) cases of Bw4/4 homozygote,38 cases (44.2 ％) of Bw4/6 heterozygote and 19 (22.1％) cases of Bw6/6 homozygote.The HCV RNA levels in Bw4/4 group,Bw4/6 group and Bw6/6 group were (3.98±0.32),(5.22±0.29),(5.04±0.38) lg IU/mL,respectively.The HCV RNA level in Bw4/4 group was significantly lower than those in the other two groups (t=2.821,P=0.0063 ; t =2.106,P =0.0407,respectively).The spontaneous clearance rates of Bw4/4 group,Bw4/6 group and BW6/6 group were 58.6％,26.3％ and 21.0％,respectively.The spontaneous clearance rate of Bw4/4 group was significantly higher than those of Bw4/6 group and Bw6/6 group (x2 =7.135,P =0.008; x2 =6.583,P =0.010,respectively).HCV infected individuals with homozygous epitopes of Bw4/4 had 4.351 times higher probability of spontaneous viral clearance than that of Bw4/6 heterozygote or Bw6/6 homozygote (OR=4.351,95％CI:1.676-11.294).Conclusions Homozygosity for HLA-Bw4-bearing B alleles is associated with significant lower HCV viral load and higher spontaneous clearance rate.The HLA-Bw4 epitopes have a protective effect against HCV infection.

Preparation and Characterization of Monoclonal Antibody Specific to PfCP-2.9 Chimeric Protein of Plasmodium falciparum / 中国寄生虫学与寄生虫病杂志

Objective To prepare and characterize monoclonal antibody against a malaria vaccine candidate, PfCP-2.9 chimeric protein of Plasmodium falciparum. Methods BALB/c mice were immunized with PfCP-2.9,and the spleen cells were used for fusion with SP2/0 cells. The monoclonal antibodies were analyzed by ELISA,Western blotting as well as growth inhibition assay. Result A monoclonal antibody was obtained. It interacted with the PfCP-2.9 recombinant protein by ELISA and Western blotting. The interaction of the monoclonal antibody with the protein was reduction-sensitive,indicating that the antibody recognized a conformational epitope. Moreover,the antibody also recognized the cultured parasites of P.falciparum by indirect immunofluorescent antibody test(IFA). When tested by growth inhibition assay,the antibody significantly inhibited parasite growth in vitro of 56% inhibition rate at the antibody concentration of 0.3 mg/ml. Conclusion A monoclonal antibody against PfCP-2.9 malaria vaccine candidate has been obtained,which recognizes a conformational epitope of the protein and natural protein.