Jiri Mestecky

Jiri Mestecky
University of Alabama at Birmingham | UAB · Department of Microbiology

M.D., Ph.D.

About

489
Publications
18,602
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21,054
Citations
Citations since 2016
35 Research Items
4228 Citations
20162017201820192020202120220200400600
20162017201820192020202120220200400600
20162017201820192020202120220200400600
20162017201820192020202120220200400600

Publications

Publications (489)
Article
Full-text available
SARS-CoV-2 is primarily an airborne infection of the upper respiratory tract, which on reaching the lungs causes the severe acute respiratory disease, COVID-19. Its first contact with the immune system, likely through the nasal passages and Waldeyer’s ring of tonsils and adenoids, induces mucosal immune responses revealed by the production of secre...
Article
Background: IgA nephropathy (IgAN) primary glomerulonephritis is characterized by the deposition of circulating immune complexes composed of polymeric IgA1 molecules with altered O-glycans (Gd-IgA1) and anti-glycan antibodies in the kidney mesangium. The mesangial IgA deposits and serum IgA1 contain predominantly λ light (L) chains, but the nature...
Article
Full-text available
The mucosal immune system is the largest component of the entire immune system, having evolved to provide protection at the main sites of infectious threat: the mucosae. As SARS-CoV-2 initially infects the upper respiratory tract, its first interactions with the immune system must occur predominantly at the respiratory mucosal surfaces, during both...
Article
Full-text available
Mucosal surfaces are colonized by highly diverse commensal microbiota. Coating with secretory IgA (SIgA) promotes the survival of commensal bacteria while it inhibits the invasion by pathogens. Bacterial coating could be mediated by antigen-specific SIgA recognition, polyreactivity, and/or by the SIgA-associated glycans. In contrast to many in vitr...
Article
Full-text available
IgA nephropathy (IgAN) is the dominant type of primary glomerulonephritis worldwide. However, IgAN rarely affects African Blacks and is uncommon in African Americans. Polymeric IgA1 with galactose-deficient hinge-region glycans is recognized as auto-antigen by glycan-specific antibodies, leading to formation of circulating immune complexes with nep...
Conference Paper
Secretory IgA (S-IgA) contributes to protecting mucosal surfaces from pathogenic bacteria attachment. It is not clear, if S-IgA interacts with microorganisms through antigen-specific Fab moiety, or antigen-nonspecifically through remaining protein backbone or through attached mostly N-oligosaccharides. Entheropahogenic E. coli (EPEC) strain O55 ca...
Article
Full-text available
Aims: Epstein-Barr virus (EBV) targets predominantly B cells and these cells could acquire new phenotype characteristics. Here we analyzed whether EBV-infected and -uninfected B cells from healthy subjects differ in proportion of dominant phenotypes, maturation stage, and homing receptors expression. Methods: EBV-infected and -uninfected cells w...
Chapter
Although the immune compartment of the genital tract is considered a component of the common mucosal system, it displays distinct features characteristic of its physiological and immunological needs not shared by other mucosal sites. These include marked differences in the phenotypes of epithelial cells, lymphocytes, macrophages and dendritic cells...
Article
Full-text available
Background/aims: IgA nephropathy is associated with aberrant O-glycosylation of IgA1, which is recognized by autoantibodies leading to the formation of circulating immune complexes. Some of them, after deposition into kidney mesangium, trigger glomerular injury. In patients with active disease nonresponding to angiotensin-converting enzyme inhibit...
Article
Full-text available
Mechanisms responsible for natural control of human immunodeficiency type 1 (HIV) replication in elite controllers (EC) remain incompletely defined. To determine if EC generate high quality HIV-specific IgA responses, we used Western blotting to compare the specificities and frequencies of IgA to HIV antigens in serum of gender-, age- and race-matc...
Data
CD4 T cell counts and length of time on HAART. (PDF)
Data
Within group differences in IgA responses to HR1 peptides. (PDF)
Data
Reactivity of IgG to HIVIIIB proteins. The percentage of infected subjects positive for IgG antibodies to each HIV protein was determined by WB using T1 and T2 serum samples. *p < 0.05 using the Fisher's exact test. (TIFF)
Data
Magnitude of IgG responses to gp70-V1V2 proteins with sequences representative of HIV Clades A, B and C. The IgG sp. act. to gp70 scaffolded proteins with V1V2 sequences representative of (A) Clade B, (B) Clade C and (C) Clade A was measured using ELISA. Within each group, the same symbol is used to designate each subject. Dashed lines represent th...
Data
Correlation between HIV-specific IgA and IgG responses. The IgA and IgG sp. act. measured to gp120, gp41BAL, and p24 at T1 and T2 was compared for subjects within each infection group using logarithmically transformed values and the two-tailed Spearman Rank correlation test. Correlation coefficients and p values obtained are shown in each graph. In...
Data
Avidity of anti-HIV IgA and IgG antibodies at T1 and T2. The avidity indices for IgG (left panel) or IgA (right panel) antibodies to (A) gp120, (B) gp41BAL, (C) p24 and (D) gp70-V1V2 at T1 and T2 are depicted in minimum-to-maximum whisker box plots. The number of subjects with antibody concentrations high enough for avidity analysis at both time po...
Data
Magnitude of the C1-specific IgA response using BAMA. The fluorescence intensity (FI) measured for IgA using 1/100 dilutions of IgG-depleted T2 serum samples and magnetic beads labeled with the C1 peptide MHEDIISLWDESLKPCVKLTPLCV was divided by the total IgA in the diluted serum. This value was then multiplied by the volume of serum tested (50 μl)...
Data
Domination of the HIV-specific humoral response by IgG. For each infected subject, the (A) IgG or (B) IgA sp. act. measured against gp120, gp41BAL or p24 was divided by the corresponding mean sp. act. of Neg controls to determine the IgG and IgA responses in infected individuals. Black symbols and lines represent medians. The magnitude of antibody...
Data
Correlation analysis of HIV-specific IgA and IgG antibody avidities. The avidity indices measured for gp120, gp41BAL and p24-specific IgA and IgG at T1 and T2 within each group were compared using the Spearman rank correlation test. Significant differences are indicated by p values and correlation coefficients in the graphs. ns: not significant. (T...
Article
Full-text available
HIV-1 infection is associated with an early and profound depletion of mucosal memory CD4⁺ T cells, a population that plays an indispensable role in the regulation of isotype switching and transepithelial transport of antibodies. In this study, we addressed whether the depletion of CD4⁺ T cell in HIV-1-infected individuals results in altered humoral...
Data
Protein microarray analysis of plasma IgG responses specific to intestinal microbial antigens. Comparison of responses to individual mucosal microbial antigens in healthy donors versus ART-naïve HIV-1-infected non-controlling (NC) individuals. Data are presented as means ± SEM; * p < 0.05; ** p < 0.01. (TIF)
Data
Concentrations of immunoglobulins specific for representative bacterial and food antigens in plasma and intestinal secretions of HIV-1-infected ART-treated and -untreated subjects. Individual plots represent the levels of immunoglobulins specific for lipopolysaccharide (LPS) expressed by Salmonella typhi or Escherichia coli, flagellins A4 FLA2 and...
Data
Normalized levels of immunoglobulins specific for common mucosal bacterial and food antigens in plasma, rectal wash, and saliva of HIV-1-infected ART-treated and untreated individuals. Levels of specific immunoglobulins in plasma (A), rectal wash (B), and saliva (C) are presented as ng / μg of total immunoglobulin of the relevant class. Error bars...
Data
CD38 expression on naïve (Tn), central memory (Tcm), effector (Tef), and effector memory (Tem) CD8+ (A) and CD4+ (B) T cells. (TIF)
Data
Heatmap representation of absolute concentrations of immunoglobulins specific for common mucosal bacterial and food antigens in plasma, rectal wash, and saliva of HIV-1-infected ART-treated and untreated individuals normalized to healthy donors. (TIF)
Article
Full-text available
Background:Tissue resident memory T cells (TrM) provide an enhanced response against infection at mucosal surfaces, yet their function has not been extensively studied in humans, including the female genital tract (FGT). Methods: Using polychromatic flow cytometry, we studied TrM cells, defined as CD62L-CCR7-CD103+CD69+ CD4+ and CD8+ T cells in mu...
Article
IgA nephropathy (IgAN) is an autoimmune disease characterized by mesangial deposition of immune complexes containing polymeric IgA1 (pIgA1) with abnormally low galactose content in oligosaccharides linked by O-glycosidic bond to the hinge region of pIgA1 molecule (Gd-pIgA1). Immune complexes are formed probably in the circulation after recognition...
Article
IgA nephropathy (IgAN) is the most common primary glomerulonephritis. In the complex pathogenesis of this disease plays a significant role, the production of specific antibodies against the abnormally glycosylated forms of immunoglobulin A1. Course of IgAN is highly variable, kidney function progressively worsens in 40 % of patients, and about half...
Article
IgA nephropathy (IgAN) is the most common type of glomerulonephritis. Its etiology involves an increased production of polymeric immunoglobulin A1 with an abnormal composition of some carbohydrate chains. The reaction of these abnormal forms of IgA1 with specific autoantibodies while circulating immune complexes arise and settle in the renal mesang...
Article
IgA nephropathy (IgAN) is the leading cause of primary glomerulonephritis in the world. The disease is characterized by the presence of immune complexes in the circulation and in mesangial deposits with ensuing glomerular injury. Although in humans there are two IgA subclasses, only IgA1 molecules are involved. The exclusivity of participation of I...
Article
The prevalent human papillomaviruses (HPVs) infect human epithelial tissues. Infections by the mucosotropic HPV genotypes cause hyperproliferative ano-genital lesions. Persistent infections by high-risk (HR) HPVs such as HPV-16, HPV-18 and related types can progress to high grade intraepithelial neoplasias and cancers. Prophylactic HPV vaccines are...
Article
Full-text available
IgA nephropathy (IgAN) is the most common primary glomerulonephritis, frequently leading to end-stage renal disease, as there is no disease-specific therapy. IgAN is diagnosed from pathological assessment of a renal biopsy specimen based on predominant or codominant IgA-containing immunodeposits, usually with complement C3 co-deposits and with vari...
Chapter
IgA nephropathy (IgAN), a frequent cause of end-stage renal disease, is an autoimmune disease wherein immune complexes consisting of IgA1 with galactose-deficient O-glycans (Gd-IgA1; autoantigen) and anti-glycan autoantibodies deposit in the glomeruli and induce renal injury. Serum IgA1 has three to six clustered O-glycans, some of which may be def...
Article
Full-text available
There have been encouraging results for the development of an effective HIV vaccine. However, many questions remain regarding the quality of immune responses and the role of mucosal antibodies. We addressed some of these issues by using a simian immunodeficiency virus (SIV) DNA vaccine adjuvanted with plasmid-expressed mucosal chemokines combined w...
Chapter
This chapter serves as an introduction to the book and presents an overview of the mucosal immune system, its major components and functions, and its unique significance with respect to the maintenance of homeostasis and health. Of particular importance is its role in maintaining the commensal microbiota that colonizes most mucosal surfaces, while...
Book
Mucosal Immunology, now in its fourth edition, is the only comprehensive reference covering the basic science and clinical manifestations of mucosal immunology. Most infectious agents enter the body through the various mucous membranes, and many common infections take place in or on mucous membranes, making this subject an area of singular importan...
Article
Full-text available
Background: Periodontitis is a chronic inflammatory disease initiated by a synergistic and dysbiotic microbial community that elicits a gingival inflammatory response leading to tissue breakdown. Periodontitis shares many characteristics with other chronic inflammatory diseases, including abnormal glycosylation of immunoglobulin (Ig)G. The current...
Article
Full-text available
Background HIV-1 entry into host cells is mediated by interactions between the virus envelope glycoprotein (gp120/gp41) and host-cell receptors. N-glycans represent approximately 50% of the molecular mass of gp120 and serve as potential antigenic determinants and/or as a shield against immune recognition. We previously reported that N-glycosylation...
Article
Full-text available
Immunoglobulin A (IgA) nephropathy (IgAN), the leading cause of primary glomerulonephritis, is characterized by IgA1-containing immunodeposits in the glomeruli. IgAN is a chronic disease, with up to 40% of patients progressing to end-stage renal disease, with no disease-specific treatment. Multiple studies of the origin of the glomerular immunodepo...
Article
Although sera and all external secretions contain antibodies to human immunodeficiency virus (HIV), their levels, specificity, isotypes, and relevant effector functions display a great degree of variability. Antibodies that bind HIV antigens and neutralize the virus are predominantly associated with the IgG isotype in sera and in all external secre...
Article
Full-text available
Author Summary HIV-1 causes a sexually transmitted disease. However, the mechanisms employed by the virus to cross genital tract tissue and establish infection are uncertain. Since cervicovaginal fluid is acidic and HIV-1 in cervicovaginal fluid is likely coated with antibodies, we explored the effect of low pH and HIV-1-specific antibodies on tran...
Article
Full-text available
IgA nephropathy (IgAN) patients have elevated serum levels of immune complexes consisting of IgA1 with galactose-deficient hinge-region O-glycans (Gd-IgA1) and anti-glycan IgG. These immune complexes deposit in the kidney and activate mesangial cells. To confirm that the activity of these immune complexes depends on the interaction of Gd-IgA1 with...
Article
Full-text available
Although human immunodeficiency virus type 1 (HIV-1)-specific antibodies are detectable in external secretions by ELISA and western blot (WB), the presence of HIV-1 neutralizing antibodies is difficult to evaluate due to the low levels of immunoglobulins (Ig) and the presence of humoral factors of innate immunity. The objective of this study was to...
Article
Studies of molecular and cellular interactions involved in the pathogenesis of IgA nephropathy have revealed the autoimmune nature of this most common primary glomerulonephritis. In patients with this disease, altered glycan structures in the unique hinge region of the heavy chains of IgA1 molecules lead to the exposure of antigenic determinants, w...
Article
IgA nephropathy, described in 1968 as IgA-IgG immune-complex disease, is an autoimmune disease. Galactose-deficient IgA1 is recognized by unique autoantibodies, resulting in the formation of pathogenic immune complexes that ultimately induce glomerular injury. Thus, formation of the galactose-deficient IgA1-containing immune complexes is a critical...
Article
Full-text available
Studies of T cell-mediated immunity in the human female genital tract have been problematic due to difficulties associated with the collection of mucosal samples. Consequently, most studies rely on biopsies from the lower female genital tract or remnant tissue from hysterectomies. Availability of samples from healthy women is limited, as most studi...
Article
IgA is the most abundantly produced antibody and plays an important role in the mucosal immune system. Human IgA is represented by two isotypes, IgA1 and IgA2. The major structural difference between these two subclasses is the presence of nine potential sites of O-glycosylation in the hinge region between the first and second constant region domai...
Article
Full-text available
Here we discuss recent advances in understanding the biochemical, immunologic, and genetic pathogenesis of IgA nephropathy, the most common primary glomerulonephritis. Current data indicate that at least four processes contribute to development of IgA nephropathy. Patients with IgA nephropathy often have a genetically determined increase in circula...
Article
Full-text available
Circulating immune complexes (CIC) containing galactose (Gal)-deficient IgA1 from adults with IgA nephropathy (IgAN) induce proliferation of cultured mesangial cells, but activities of CIC from pediatric patients with the disease have not been studied. CIC of different sizes were isolated from sera of pediatric and adult IgAN patients and their eff...
Article
IgA nephropathy (IgAN), the most common glomerulonephritis, is characterized by mesangial IgA1-containing immunodeposits, proliferation of mesangial cells, and matrix expansion. Clinical onset is frequently heralded by synpharyngitic hematuria, macroscopic hematuria during an upper-respiratory tract infection. Clinical and laboratory data support a...
Article
INTRODUCTION AND AIMS: Idiopathic retroperitoneal fibrosis (IRF) is a rare immune-mediated condition characterised by a fibro-inflammatory periaortic tissue which often entraps the ureters and may cause acute renal failure. IRF is histologically characterized by marked fibrosis, lympho-plasmacellular inflammation and eosinophil infiltration. A caus...
Article
Mucosal immune system is functionally characterized by its ability to limit the access of environmental antigens such as food, airborne materials, and commensal microbes to the systemic immune compartment, leading to reduction in the magnitude of systemic immune responses. Mucosal immune system reacts at the site of antigen exposure and at anatomic...
Article
Full-text available
Keyhole limpet haemocyanin (KLH) appears to be a promising protein carrier for tumor antigens in numerous cancer vaccine candidates. The humoral immune response to KLH was characterized at the single-cell level with ELISPOT combined with separations of cell populations according to their expression of homing receptors (HRs). The analysis of HR expr...
Article
IgA nephropathy (IgAN) is characterized by the deposition of IgA1 in kidney mesangia and the presence of IgA1-containing immune complexes in the circulation. Structural studies of IgA1 isolated from sera of IgAN patients indicated a statistically significant decrease in the content of galactose (Gal). Using a combination of lectins specific for gly...
Article
Full-text available
IgA nephropathy (IgAN) is the most common primary glomerulonephritis in the world. Aberrantly glycosylated IgA1, with galactose (Gal)-deficient hinge region (HR) O-glycans, plays a pivotal role in the pathogenesis of the disease. It is not known whether the glycosylation defect occurs randomly or preferentially at specific sites. We have described...
Article
Citation Mestecky J, Alexander RC, Wei Q, Moldoveanu Z. Methods for evaluation of humoral immune responses in human genital tract secretions. Am J Reprod Immunol 2011; 65: 361–367 The compilation of epidemiological, virological, and immunological data clearly indicates that HIV-1 infection must be considered primarily as a disease of the mucosal im...