Definition of human apolipoprotein A-I epitopes recognized by autoantibodies present in patients with cardiovascular diseases.

Autoantibodies to apolipoprotein A-I (anti-apoA-I IgG) have been shown to be both markers and mediators of cardiovascular disease, promoting atherogenesis and unstable atherosclerotic plaque. Previous studies have shown that high levels of anti-apoA-I IgGs are independently associated with major adverse cardiovascular events in patients with myocardial infarction. Autoantibody responses to apoA-I can be polyclonal and it is likely that more than one epitope may exist. To identify the specific immunoreactive peptides in apoA-I, we have developed a set of methodologies and procedures to isolate, purify, and identify novel apoA-I endogenous epitopes. First, we generated high purity apoA-I from human plasma, using thiophilic interaction chromatography followed by enzymatic digestion specifically at lysine or arginine residues. Immunoreactivity to the different peptides generated was tested by ELISA using serum obtained from patients with acute myocardial infarction and high titers of autoantibodies to native apoA-I. The immunoreactive peptides were further sequenced by mass spectrometry. Our approach successfully identified two novel immunoreactive peptides, recognized by autoantibodies from patients suffering from myocardial infarction, who contain a high titer of anti-apoA-I IgG. The discovery of these epitopes may open innovative prognostic and therapeutic opportunities potentially suitable to improve current cardiovascular risk stratification.

Linear and Continuous Flavivirus Epitopes From Naturally Infected Humans.

This manuscript is an up-to-date review of experimentally validated linear and continuous epitopes identified from arbovirus members of the Flavivirus genus. We summarized 153 immunoreactive peptides from the Dengue virus, Zika virus, Japanese encephalitis virus, West Nile virus, and tick-borne encephalitis virus described in studies published from 1989 to 2020. We included peptides from structural (envelope, capsid, and pre-membrane) and nonstructural (Ns1-5) viral proteins that demonstrated relevant immunoreactivity with antibodies from naturally infected or vaccinated humans. We included peptides that demonstrated relevant reactivity features, such as indicators of disease severity related to immunological or immunopathological outcomes, differential or group diagnostic markers, immunotherapy candidates, and potential for vaccine formulation. The majority of immunoreactive peptides were described for DENV probably due to its long-lasting impact on human health and the lack of efficient vaccines and therapeutic methods. Immune landscape data regarding linear immunoreactive and continuous flavivirus peptides are still scarce, and a complete and more detailed map remains to be elucidated. Therefore, this review provides valuable data for those investigating the antibody response against flavivirus infection.

Dietary compliance in celiac disease.

Celiac disease is an immune-mediated disorder that causes severe architectural disturbance in the small intestinal mucosa of genetically-predisposed individuals. Impaired absorption of multiple nutrients results and diarrhea and weight loss develop. Evidence has accumulated that a strict gluten-free diet can result in resolution of diarrhea, weight gain and normalization of nutrient malabsorption. In addition, histopathological changes also normalize, but this histopathological response appears to be time-dependent, sex-dependent and age-dependent. Compliance to a gluten-free diet is difficult and costly resulting in poor compliance and only a limited clinical response. This poses a risk for later long-term complications, including malignancy. A major practical clinical problem is the assessment of compliance to the gluten-free diet. Although symptoms may resolve and serological antibody markers may improve, multiple studies have documented ongoing architectural disturbance and inflammatory change, and with these continued inflammatory changes, a persistent risk for long-term complications. Recent immunological studies have suggested that peptides can be detected in both urine and fecal specimens that may be indicative of limited compliance. At the same time, multiple biopsy studies have demonstrated that complete normalization of the mucosa may occur in some patients within 6 mo of initiation of a gluten-free diet, but more often, up to 2 years or more may be required before repeated biopsies eventually show mucosal recovery and mucosal healing.