Introduction:
Hemophilia is a medical disorder defined by a lack of clotting factor 8 and clinically, there are different types of hemophilia seen. To address this, there was an increase in the use of exogenous clotting factors as a therapeutic effect. However, while they are beneficial in the treatment of hemophilia patients, the immune response to clotting factor 8 appears to be a perfectly typical and traditional response of the body to externally created antigens. However, when factor 8 is supplied by external intravenous injections, these clotting factors might become deposited in the lymphatic system and organs such as the spleen.
What Happens in Hemophilia?
As discussed earlier, hemophilia is an X-linked disorder that is seen with profuse bleeding of blood during an injury, as it occurs as a genetic disorder. Hemophilia mainly involves the X-chromosome and is seen affecting females, as in males, they act as carriers and pass it onto the female offspring. Globally, the prevalence of an X chromosome is seen at a rate of one in five thousand births per year. And in order to handle this, there was an external need for factor 8 to induce clotting. The right factor is also called the plasma coagulation factor. For management, the external factors are obtained from the blood plasma or through recombinant technology.
How Does Factor VIII Perform in the Cascade Cycle?
The clotting cascade, or body, is the cycle or series of events that take place while a clot is formed. Here, factor 8 plays a very important role as it helps in the prevention of premature clotting and stabilization of the factor at very premature levels. Because of this reason, factor eight is also called the von Willebrand factor and is commonly seen in its inactive form in the bloodstream. However, factor 8, which serves as a procoagulative agent (an agent that initiates or acts as a triggering factor to promote clotting), becomes active when in contact with the other clotting factor, factor 9, on the surface of the platelets.
What Is the Response of Factor VIII Towards Immunity?
The therapeutic effect of endogenously supplying factor eight in hemophilia patients is highly essential and immunogenic to maintain the clotting cycle. However, despite assessing the therapeutic usage of factor 8 over the past three decades through extensive research, it still does not give a clear idea of the factors affecting its efficacy. Although the physiological benefits and the way the body takes it to appreciate bleeding, the factors contributing to the development of antibodies against this externally supplied factor eight are unclear. By conducting various studies in patients with hemophilia A who show a lack of factor 8 inhibitors, the efficacy of this factor is well tolerated. Several studies hypothetically state that the reason for the attack of the body is the therapeutic factor 8, where the body sends signals often released at times of danger, making the body naturally send inflammatory mediators to attack it. Other studies state that the depleting effect on factor 8 can also be proportional to the tolerance effect of each person and their inflammatory response towards it, suppressing the tolerance factor towards therapeutic factor 8.
What Are the Factors Contributing to the Immune Response of Factor VIII?
As discussed above, the possible reasons and the effect factor eight has on the body, there are some evident factors that contribute to the efficacy and anti-inflammatory properties of factor eight, and they are:
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Dosage of the Drug: The amount of factor eight to be administered plays an important factor in understanding the correlation of the drug with its anti-inflammatory factors. Where the amount of external factor 8 administered is directly equivalent to the immune response to it.
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Alarmin Factors: The molecular pattern of the cells that are associated with the reaction towards an external substance is known as DAMP, and molecular patterns associated with pathogens (PAMP) are together known as alarmin. These factors build patterns that help in the recognition of endogenous factors, which in turn activate the inflammatory cells to identify and deplete them.
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Self-Recognition of the Immune System: Although self-recognition and identification of the cells are part of the naturally programmed clotting cycle, both the T and B lymphocytes or inflammatory cells are activated, sending the inflammatory cells to suppress the therapeutic drug delivered.
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T-Cell Modulated Factor Recognition: Here, T-cells are one of the defense cells produced by the white blood cells, more specifically, the lymphocytes. According to the studies conducted, the regulatory t-cells present in the bloodstream increase the functioning of the scarcely functioning identifiable factor 8 that is seen in correlation with the CD4+ cells.
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Recognition by Immunoglobulins: Immunoglobulins are the chief defense factors of the body, all of which are responsible for the normal functioning of the body. Here, the function of the immunoglobulin is to purify the plasma and relieve it from any anti-factor 8, inhibiting the binding of the anti-factor 8 to factor 8. Thus, it creates a natural and health-inhibitory effect on the anti-factor 8 immunoglobulin.
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Increased Immune Response or Compromised Tolerance: By closely examining a group of factors, the genes that show multiplication factors, also known as polymorphism, encode an anti-inflammatory enzyme called heme-oxygenase, which helps in developing inhibitory factors in patients with hemophilia.
Conclusion:
According to the findings of the overall investigations, the immunological response of the body to factor 8 and its newer methods impede the neutralization of alarmins or factors operating against factor 8 antibodies. This finding was reached after a series of clinical trials utilizing animal models. These revolutionary procedures make use of highly skilled techniques such as mass cytometry (cytometry is the charting of cells), immunotyping (studying the type of immunoglobulins), flow cytometry, and so on. Thus, monitoring and improving care and coordination in the management of hemophilic patients contribute to improved tolerance and immunogenicity of the externally administered therapeutic clotting factor 8. Thus, maintaining these tolerance levels of factor 8 in the body is critical for the patient to fully benefit from the supplied factor 8 replacement treatment.
