Why is C3 and C4 complement so important in the diagnosis and treatment of systemic lupus erythematosus?

What is C3 and C4 complement

Complement is a group of thermolabile, activated enzymatically active proteins present in human or vertebrate serum and tissue fluid
.
Including more than 30 kinds of soluble proteins and membrane-bound proteins, it is called the complement system
.
It is widely involved in the body's anti- infection defense response and immune regulation, and can also mediate the damage response of immune pathology.
It is an effect amplification system with important biological roles in the body
.
Overactivation of the complement system and low complement levels are common pathological changes in SLE
.
Complement C3 and C4 are important biologically active proteins of the complement system.
They are mainly synthesized by hepatocytes and macrophages.
They participate in the classical activation pathway and alternative activation pathway of complement through activation and lysis, thereby mediating the complement cascade reaction and are important in vivo.
immune activity
.

The history of complement in the SLE taxonomy

1971 ARA Classification Criteria There are no immunological indicators such as antinuclear antibodies and complement in the standard
.
1982 ARA Classification Criteria This standard has begun to use autoantibodies as an immunological standard
.
However, complement reduction was not included at this time because adding this criterion did not improve the accuracy of the criteria for this classification
.
The significance of complement is more inclined to judge clinical new events
.
1982 Beijing diagnostic criteria and 1987 Shanghai diagnostic criteria These two criteria have begun to reduce complement as a new criterion
.
1992 ACR Classification Criteria Mainly about antiphospholipid antibodies, deleted lupus cell positive, added antiphospholipid antibody positive, and defined antiphospholipid antibody positive as antiphospholipid antibody positive or lupus anticoagulant positive or syphilis lasting at least 6 months Serum false positive
.
But no criteria for complement have been added
.
2012 SLICC Standard For the first time, hypocomplementemia was included as an immunological criterion.
As long as there is low C3, low C4 or low CH50, it can be defined as hypocomplementemia.
Although some people think that this criterion cannot improve the data model for classifying SLE, complement The decrease may reflect the pathological mechanism of SLE
.
The classification criteria jointly launched by ACR & EULAR in 2017
further clarified the significance of low C3 and low C4 complements for the classification of systemic lupus erythematosus

.

related to the development of SLE disease

The determination of serum complement components in SLE patients is extremely important for diagnosis and disease observation, and has been widely used in clinical practice
.
Existing studies suggest that the SLE complement activation pathway is related to both the classical pathway and the alternative pathway
.

Low C3 and low C4 levels were significantly associated with disease activity in SLE patients

In a study of 51 patients with recurrent SLE, the correlation between SLEDAI score and serological indicators was evaluated.
The results showed that among the 51 patients with SLE recurrence, 92.
3% of the 13 patients with renal involvement had low C3 levels, Patients with low C4 levels were 84.
6%; patients without renal involvement, the proportions of patients with low C3 levels and low C4 levels were 43% and 53%, respectively
.
This indicated that low C3 and C4 levels in SLE patients were significantly associated with disease activity
.

Anti-dsDNA antibodies and low complement levels are associated with infection and disease relapse in SLE patients

One study retrospectively analyzed data from 173 hospitalizations in 142 patients, with an infection rate of 50.
6%, evaluating the site of infection, pathogens, and associated factors, with low C4 levels being an independent risk factor for infection in SLE patients
.
Another study assessed serum levels of anti-dsDNA antibodies, C1q, nucleosomes, histones, C3 and C4 complements in 175 serological samples from 99 SLE patients and 20 serum samples from healthy subjects.
Anti-dsDNA and complement levels are predictors of relapse
.

What is C3 and C4 complement

What is C3, C4 complement Complement is a group of thermolabile, activated enzymatically active proteins present in human or vertebrate serum and tissue fluid
.
Including more than 30 kinds of soluble proteins and membrane-bound proteins, it is called the complement system
.
It is widely involved in the body's anti- infection defense response and immune regulation, and can also mediate the damage response of immune pathology.
It is an effect amplification system with important biological roles in the body
.
Hyperactivation of the infectious immune complement system and low complement levels are common pathological changes in SLE
.
Complement C3 and C4 are important biologically active proteins of the complement system.
They are mainly synthesized by hepatocytes and macrophages.
They participate in the classical activation pathway and alternative activation pathway of complement through activation and lysis, thereby mediating the complement cascade reaction and are important in vivo.
immune activity
.

The history of complement in the SLE taxonomy

The development history of complement in the SLE classification standard 1971 ARA classification standard 1971 ARA classification standard 1982 ARA classification standard 1982 ARA classification standard This standard has begun to use autoantibodies as an immunological standard
.
However, complement reduction was not included at this time because adding this criterion did not improve the accuracy of the criteria for this classification
.
The significance of complement is more inclined to judge clinical new events
.
1982 Beijing Diagnostic Criteria and 1987 Shanghai Diagnostic Criteria 1982 Beijing Diagnostic Criteria and 1987 Shanghai Diagnostic Criteria These two criteria have begun to take complement reduction as a new criterion
.
1992 ACR classification standard The 1992 ACR classification standard mainly focuses on the research content of antiphospholipid antibodies, deletes lupus cell positivity, adds antiphospholipid antibody positivity, and defines antiphospholipid antibody positivity as antiphospholipid antibody positive or lupus anticoagulation Syphilis seropositive or false positive for syphilis lasting at least 6 months
.
But no criteria for complement have been added
.
2012 SLICC standard 2012 SLICC standard 2017 ACR & EULAR co-launched taxonomy 2017 ACR & EULAR co-launched taxonomy

The relationship between complement and SLE

The relationship between complement and SLE

related to the development of SLE disease

The determination of serum complement components in SLE patients is extremely important for diagnosis and disease observation, and has been widely used in clinical practice

.

In a study of 51 patients with recurrent SLE, the correlation between SLEDAI score and serological indicators was evaluated.

One study retrospectively analyzed data from 173 hospitalizations in 142 patients, with an infection rate of 50.

The 2019 EULAR guidelines state that risk factors for higher disease recurrence are younger age at onset, no use of antimalarial drugs, persistent widespread disease activity, and serological activity (anti-dsDNA antibodies, low complement levels)

Although the complement-related effective drugs for the treatment of SLE have not yet been developed, it is expected that there will be drugs targeting the complement system for the treatment of SLE in the future

Source: Rheumatism and Nephrology Channel in the Medical Community, Rheumatism Time, Chinese Journal of Practical Internal Medicine    Editor: Snow Only for doctors to learn and communicate , leave a message here