ABSTRACT
Numerous studies have focused on inflammation-related markers to understand COVID-19. In this study, we performed a comparative analysis of spike (S) and nucleocapsid (N) protein-specific IgA, total IgG and IgG subclass response in COVID-19 patients and compared this to their disease outcome. We observed that the SARS-CoV-2 infection elicits a robust IgA and IgG response against the N-terminal (N1) and C-terminal (N3) region of the N protein, whereas we failed to detect IgA antibodies and observed a weak IgG response against the disordered linker region (N2) in COVID-19 patients. N and S protein-specific IgG1, IgG2 and IgG3 response was significantly elevated in hospitalized patients with severe disease compared to outpatients with non-severe disease. IgA and total IgG antibody reactivity gradually increased after the first week of symptoms. Magnitude of RBD-ACE2 blocking antibodies identified in a competitive assay and neutralizing antibodies detected by PRNT assay correlated with disease severity. Generally, the IgA and total IgG response between the discharged and deceased COVID-19 patients was similar. However, significant differences in the ratio of IgG subclass antibodies were observed between discharged and deceased patients, especially towards the disordered linker region of the N protein. Overall, SARS-CoV-2 infection is linked to an elevated blood antibody response in severe patients compared to non-severe patients. Monitoring of antigen-specific serological response could be an important tool to accompany disease progression and improve outcomes.
Subject(s)
COVID-19 , Humans , SARS-CoV-2 , Antibodies, Viral , Immunoglobulin G , Immunoglobulin A , Immunoglobulin M , Spike Glycoprotein, CoronavirusABSTRACT
BACKGROUND: In humans, Trypanosoma cruzi infection is controlled by a complex immune response. Immunoglobulin G (IgG) is important for opsonizing blood trypomastigotes, activating the classic complement pathway, and reducing parasitemia. The trypanocidal activity of benznidazole is recognized, but its effects on the prevention and progression of Chagas disease is not well understood OBJECTIVE: We aimed to evaluate the levels of total IgG and cross-specific IgG subclasses in patients with chronic Chagas disease of different clinical forms before and after 4 years of benznidazole treatment. METHODS: Eight individuals with the indeterminate form and nine with the cardiac form who completed the treatment protocol were evaluated. The levels of total IgG and IgG1, IgG2, IgG3, and IgG4 isotypes were quantified in the serum of each individual using the fluorescent immunosorbent assay. The results are expressed as relative fluorescence unit. RESULTS: Patients with chronic Chagas disease presented decreased levels of total IgG at 48 months after benznidazole treatment. Increased IgG1 and decreased IgG3 levels were observed in patients with the cardiac form and those with exacerbated clinical forms. In addition, a decrease in the IgG3/IgG1 ratio was observed in individuals with the cardiac form of Chagas disease. CONCLUSIONS: Benznidazole administration in the chronic phase differentially changes IgG subclasses in patients with cardiac and indeterminate forms, and monitoring the IgG3 level may indicate the possible prognosis to the cardiac form or worsening of the already established clinical form.
Subject(s)
Chagas Disease , Nitroimidazoles , Chagas Disease/drug therapy , Humans , Immunoglobulin G , Nitroimidazoles/therapeutic use , ParasitemiaABSTRACT
Antibody levels to some periodontal pathogens are associated with enhanced levels of inflammatory markers. The purpose of the current study was to examine the relative contribution of serum immunoglobulin G (IgG) subclass antibody level factors and local factors on the probing pocket depth in chronic periodontitis. Serum samples were taken from 444 patients diagnosed with moderate and severe periodontitis and 223 control subjects. The IgG subclass antibody titers to Porphyromonas gingivalis (Pg), Aggregatibacter actinomycetemcomitans (Aa) and Tanerella forsythia (Tf) using indirect immunoassay (ELISA) were determined. The relative contribution of patient, tooth and site-associated parameters on the probing pocket depth were evaluated with a hierarchical multilevel model. The results indicated that periodontitis patients had detectable levels of IgG1 and IgG2. High IgG1 and IgG2 antibody levels against Aa occurred in 132 and 142 periodontitis patients, respectively. High IgG1 and IgG2 antibody levels against Pg occurred in 141 and 138, periodontitis patients, respectively, and High IgG1 and IgG2 antibody levels against Tf occurred in 121 and 136 periodontitis patients, respectively. The majority of the variance was attributed to the site level (48 percent). The multilevel analysis associated deeper probing depth with subject factors (serum IgG1 and IgG2 antibody to Pg and Aa), tooth factors (tooth type), and site factors (mesial-distal location and bleeding on probing). Elevated serum IgG1 and IgG2 antibody to Pg and Aa (subject factors) reflects destructive periodontal disease status.
Los niveles de anticuerpos en algunos patógenos periodontales están asociados con mayores niveles de marcadores inflamatorios. El propósito de este estudio fue examinar la contribución relativa de inmunoglobulina sérica G (IgG) factores de nivel de anticuerpos de subclase y factores locales en la profundidad del sondaje en periodontitis crónica. Se tomaron muestras de suero de 444 pacientes con diagnóstico de periodontitis moderada y grave y de 223 sujetos de control. Se determinaron los títulos de anticuerpos IgG subclase a Porphyromonas gingivalis (Pg), Aggregatibacter actinomycetemcomitans (Aa) y Tanerella forsythia (Tf) mediante inmunoensayo indirecto (ELISA). La contribución relativa de los pacientes, los dientes, y el sitio asociado a los parámetros en la profundidad de sondaje fueron evaluados con un modelo multinivel jerárquico. Los resultados indicaron que los pacientes con periodontitis tenían niveles detectables de IgG1 e IgG2. Altos niveles de anticuerpos IgG1 e IgG2 contra Aa fueron observados en 132 y 142 pacientes con periodontitis, respectivamente. Niveles altos de anticuerpos IgG1 e IgG2 contra Pg fueron detectados en 141 y 138 en pacientes con periodontitis respectivamente, y niveles altos de anticuerpos IgG1 e IgG2 contra Tf se produjeron en 121 y 136 pacientes con periodontitis, respectivamente. La mayor parte de la varianza se atribuyó a nivel de sitio (48 por ciento). El análisis multinivel asociados a profundidad de sondaje con factores relacionados a los sujetos, anticuerpos (suero IgG1 e IgG2 Aa y Pg), factores de los dientes (tipo) y los factores del sitio (localización mesial - distal y sangrado al sondaje). Anticuerpos elevados de suero IgG1 e IgG2 Aa y Pg (factores de los sujetos) reflejan el estado de la enfermedad periodontal destructiva.
Subject(s)
Humans , Male , Adult , Female , Middle Aged , Immunoglobulin G , Chronic Periodontitis/immunology , Chronic Periodontitis/microbiology , Antibodies , Aggregatibacter actinomycetemcomitans/immunology , Enzyme-Linked Immunosorbent Assay , Multilevel Analysis , Porphyromonas gingivalis/immunology , Regression Analysis , Risk AssessmentABSTRACT
Se estudiaron 45 pacientes asmáticos adultos de difícil manejo, de más de 5 años de evolución, 37 de ellos esteroide dependientes y 8 no dependientes, con asma alérgica o intrínseca y algunos con infecciones respiratorias recurrentes de predominio viral. Por nefelometría se midieron los niveles séricos de las Igs G, M y A, y por ELISA se determinó la IgE total. Se encontraron 4 pacientes con deficiencia de IgG total, en el grupo de los esteroide dependientes. Mediante ELISA tlpo sandwich y con anticuerpos monoclonales específicos para las subclases de IgG se investigaron los niveles séricos de IgG1, 2, 3 y 4. En el 55.6 por ceinto de los enfermos se encontraron una O más deficiencias de subclases. No hubo diferencias significativas entre los grupos esteroide y no esteroide dependientes, ni entre los asmáticos alérgicos e intrínsecos, ni entre los con infección recurrente o sin ella. Predominó la deficiencia de IgG1; en total el 46.7 por ciento de los pacientes tenían deficiencia aislada o combinada de IgG1, el 31.1 por ciento de IgG2, el 24.4por ciento de IgG3 y el 17.8 por ciento de Igd4. La alta incidencia de deficiencia de subclases podría deberse a la acción de los esteroides o a una alteración en la regulación de la síntesis de Igs producida por un defecto Inmune primario. Esta deficiencia sería la responsable del comportamiento agresivo de la enfermedad
We studied 45 adult asthmatic patients with difficult to care disease and who had more than five years of evolution; they suffered from elther allergic or intrinsic asthma and some had experienced recurrent respiratory tract infections. predominantly of viral etiology. Serum levels of IgA, IgG and IgM were measured by nephelometry and total lgE was determined by an Enzyme-Linked immunosorbent Assay (ELISA). Total lgG deficiency was found in four steroid. dependent patients. Serum levels of IgG subclasses 1 to 4 were measured by means of a sandwich-like ELISA with specific monoclonal antibodies. One or more subclass deficiencies were present In 55.6% of the patients. Significant differences were not found between the following groups: steroid and nonsteroid dependent patients; allergic or intrinsic, asthma; and individuals with or without history of infection. IgG 1 deficiency was the most commonly found: It was present in 46.7% of the patients, either as an isolated disorder or combined with alteration of other subclasses. Deficiency of other subclasses was present in the following proportions: 31.1% for IgG2; 24.4% for IgG3 and 17.8 for IgG4. The high incidence of subclass deficiency may be due to steroid action or to primary Immune defects leading to disorders of IgG synthesis. Such situation might be responsible for the aggressive behavior of the disease