The immune system, which aids in defending the body against illness and infection, includes the complement system as a crucial component. It is made up of a number of proteins that cooperate to identify and eliminate outside invaders. The classical pathway is one of the pathways of the complement system, and it is responsible for triggering the activation of the complement proteins. In some cases, this pathway can become overactive and lead to pathogenic complement activation, which can cause a variety of diseases, including membranous nephropathy. We shall talk about how pathogenic complement activation in membranous nephropathy is triggered via the classical pathway in this post.

What is the Classical Pathway?

The complement system has several routes, including the classical pathway. It is in charge of spotting and eliminating invaders from outside the body, like bacteria and viruses. An antibody—a protein made by the immune system to identify and combat foreign invaders—binds to an antigen, activating the classical route. The activation of the complement proteins is brought on by this interaction, and the proteins then cooperate to identify and eliminate the foreign invader.

Many proteins, including C1, C2, C3, C4, and C5, make up the classical route. Together, these proteins are able to identify and eliminate invading foreign substances. The antigen-antibody combination is bound by protein C1, which is the first in the process. The C3 convertase complex is created when C2 and C3 join forces with C1 at this point. C3 then splits into C3a and C3b as a result of this complication. The C5 convertase is created when C3b attaches to the antigen-antibody complex and is joined by C4 and C5. C5 then splits into C5a and C5b as a result of this complicated. When C5b attaches to the antigen-antibody complex, the membrane assault complex, which is in charge of eliminating the invading foreign object, is subsequently formed.

What is Membranous Nephropathy? 

A malfunctioning protein buildup in the glomerular membrane is the root cause of Membranous Nephropathy (MN), a kidney condition. High blood pressure and edoema are only a couple of the issues it can bring, in addition to poor blood filtration. Medication and lifestyle changes, such as consuming less salt and maintaining a healthy weight, are frequently used to treat MN. In some circumstances, surgery may be required to improve kidney function and relieve symptoms. The key to controlling MN is early identification and treatment because, if untreated, the condition can result in irreparable kidney damage.

The thickening of a section of the glomerular basement membrane is the primary cause of membraneous nephropathy. The kidneys have a membrane called the glomerular basement membrane that aids in removing waste and surplus fluid from circulation. A normal glomerular function is impaired by the thicker membrane. As a result, a significant amount of protein is excreted in the urine.

One of the most typical causes of nephrotic syndrome is this illness. This is a collection of symptoms that also includes edoema, low blood protein levels, high cholesterol, high triglyceride levels, and protein in the urine. Membranous nephropathy may be a secondary or comorbid disorder, or it may be a primary kidney disease.

The following increase your risk for this condition:

-Cancers, especially lung and colon cancer

-Exposure to toxins, including gold and mercury

-Infections, including hepatitis B, malaria, syphilis, and endocarditis

-Medicines, including penicillamine, trimethadione, and skin-lightening creams

-Systemic lupus erythematosus, rheumatoid arthritis, Graves disease, and other autoimmune disorders

The disorder occurs at any age but is more common after age 40.

How Does the Classical Pathway Trigger Pathogenic Complement Activation in Membranous Nephropathy?

Membranous nephropathy (MN) is a form of kidney disease in which the basement membrane of the glomerulus thickens, causing greater protein loss in the urine and potentially irreversible kidney damage. It is believed that the pathophysiology of this condition is due to the classical pathway of complement activation.

The pathogenic complement can be activated in specific situations when the classical route is hyperactive. This can happen when the complement proteins do not properly detect the antigen-antibody complex, which can result in the development of the C5 convertase without the necessary cleavage of C3 and the subsequent creation of the C5 convertase. The body’s cells and tissues may suffer harm as a result of the membrane assault complex that may result from this.

The membrane assault complex is then formed by the interaction of C5b with C6, C7, C8, and a number of additional proteins. This combination has the capacity to pierce host cell membranes and result in cell lysis. The glomerular basement membrane in MN is hypothesized to be harmed by the membrane assault complex, increasing urine protein loss and ultimately resulting in kidney failure.

One of the diseases that can be caused by pathogenic complement activation is membranous nephropathy. This is a type of kidney disease that is caused by the formation of a thick membrane in the kidneys. This membrane has the potential to harm the kidneys and cause renal failure. The overactivation of the classical pathway, which prompts the development of the membrane assault complex, results in the production of this membrane. The kidneys’ cells and tissues are then damaged by this combination, which causes the creation of a thick membrane.

In conclusion, it is believed that the pathophysiology of membranous nephropathy results from the conventional pathway of complement activation. The creation of the membrane assault complex, which can breach the basement membrane of the glomerulus and result in cell injury and protein loss in the urine, initiates this pathway when antigen-antibody complexes bind to receptors on the surface of host cells.


The complement system, which assists in defending the body against infection and disease, includes the classical pathway as a crucial component. Membranous nephropathy and other illnesses, including those caused by pathogenic complement activation, can be brought on in some situations by an overactive route in this system. In this essay, we covered the topic of how the harmful complement activation in membranous nephropathy results from the classical pathway. We talked about how the classical pathway is made up of many proteins that cooperate to detect and exterminate alien intruders. We also talked about how an overactive classical route can result in the production of the membrane assault complex, which can harm the kidneys’ cells and tissues and result in the development of a thick membrane.

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