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The complement system is a group of approximately 20 plasma proteins that strengthen the body's defenses against infections through opsonization, inflammation, and cell lysis. Opsonization involves coating pathogens with complement proteins, making them more recognizable and facilitating phagocyte engulfment. Certain complement proteins induce inflammation that attracts immune cells to the site of infection. Cell lysis involves the destruction of pathogens through the formation of a...
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A complementation test is a simple cross to identify whether the two mutations are located on the same gene or different genes. It was first performed by Edward Lewis in the 1940s while working on fruit flies. He developed the test to identify the location and arrangement of different mutations on chromosomes.
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Relative risk (RR) is a statistical measure commonly used in epidemiology to compare the likelihood of a particular event occurring between two groups. This metric is important for evaluating the relationship between exposure to a specific risk factor and the probability of a particular outcome. It plays a crucial role in medical research, public health studies, and risk assessment. Relative risk quantifies how much more (or less) likely an event is to occur in an exposed group compared to an...
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The hosts' susceptibility to infection depends on several factors. The integrity of the skin and mucous membranes helps protect the body against microbial attacks. When the skin is altered, the chance of infection, limb loss, and even death increases.
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Flood risk assessment involves careful planning and analysis to ensure the safety of communities near water retention structures. Capacity contours are a vital tool in this process, as they illustrate the potential spread of water at specific levels in a given area. In the context of building a bund across a small valley, these contours play a critical role in evaluating the safety of nearby residential areas.In this example, the bund is intended to store stormwater in the valley. The engineers...
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Gene transcription is regulated by the synergistic action of several proteins that form a complex at a gene regulatory site. This is observed in eukaryotes, where the regulation of gene expression is a complex process. Regulatory proteins in eukaryotes can broadly be classified into two types – regulators that bind directly to specific DNA sequences and co-regulators that associate with regulatory proteins but cannot directly bind to the DNA. These co-regulators are further divided into...
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Haplotype CFHR3*B, activación del complemento y riesgo de nefropatía por IgA

Yongji Zhang1, Honghong Zou1,2, Xinran Ni1

  • 1Renal Division, Department of Medicine, Peking University First Hospital; Peking University Institute of Nephrology; Key Laboratory of Renal Disease (Peking University), National Health Commission; Key Laboratory of Chronic Kidney Disease Prevention and Treatment, Ministry of Education; State Key Laboratory of Vascular Homeostasis and Remodeling, Peking University and NHC Key Laboratory of Cardiovascular Molecular Biology and Regulatory Peptides; Beijing, 100034, China.

Journal of the American Society of Nephrology : JASN
|January 21, 2026
PubMed
Resumen

El haplotipo CFHR3*B aumenta el riesgo de nefropatía por IgA al mejorar la activación del complemento. Esta variante eleva los niveles y la función de la proteína 3 relacionada con el Factor H (FHR3), promoviendo la progresión de la enfermedad.

Palabras clave:
nefropatía por IgAhaplotipo CFHR3*Bactivación del complementoFHR3genéticainmunología

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Área de la Ciencia:

  • Inmunología
  • Genética
  • Nefrología

Sus antecedentes:

  • La activación del complemento juega un papel en la nefropatía por IgA (IgAN).
  • Estudios previos vincularon la deleción de CFHR3/CFHR1 con la protección contra la IgAN.
  • El haplotipo CFHR3*B se asocia con una mayor transcripción de CFHR3 y un mayor riesgo de síndrome urémico hemolítico atípico.

Objetivo del estudio:

  • Investigar la asociación entre el haplotipo CFHR3*B y la susceptibilidad a la nefropatía por IgA.
  • Determinar el impacto funcional del haplotipo CFHR3*B en la regulación del complemento y la transcripción de CFHR3.

Principales métodos:

  • Análisis genético de 1108 pacientes con IgAN y 630 controles.
  • Ensayos de actividad de luciferasa para evaluar la actividad transcripcional de CFHR3.
  • Análisis de proteína recombinante de la variante codificante rs138675433 (FHR3241Ser).

Principales resultados:

  • El haplotipo CFHR3*B y el genotipo CFHR3*BB fueron más frecuentes en pacientes con IgAN.
  • El genotipo CFHR3*BB se correlacionó con niveles más bajos de C3 y un aumento de la deposición de C3 glomerular.
  • El haplotipo CFHR3*B mejoró la transcripción de CFHR3, siendo rs446868 la variante funcional.
  • La variante FHR3241Ser mostró una mayor unión a C3b y desregulación del Factor H, acelerando la activación del complemento y la hemólisis.
  • FHR3241Ser aumentó la activación del complemento inducida por la deposición de IgA en células mesangiales.

Conclusiones:

  • El haplotipo CFHR3*B es una variante de susceptibilidad para la nefropatía por IgA.
  • Este haplotipo acelera la activación del complemento a través de la transcripción mejorada (rs446868A) y la función aumentada de FHR3 (rs138675433T).
  • Estos hallazgos dilucidan un nuevo mecanismo que vincula la desregulación del complemento con la patogénesis de la IgAN.