Dermatomyositis (DM) is an autoimmune inflammatory disease that targets the body’s skeletal muscles and skin. This leads to inflammation and progressive muscle weakness. Intravenous Immunoglobulin (IVIG) is a therapeutic blood product composed of concentrated antibodies derived from the plasma of thousands of healthy donors. This treatment is used to manage various immune deficiencies and autoimmune disorders, including DM.
The Immune System Dysfunction in Dermatomyositis
The tissue damage in dermatomyositis is driven by microangiopathy, which involves the deposition of immune complexes that activate the body’s complement system. The complement cascade is a sequence of proteins that, when activated, work to tag pathogens for destruction and directly lyse cells.
In DM, the activated complement proteins target the endothelial cells lining the muscle capillaries. The cascade culminates in the formation of the Membrane Attack Complex (MAC), a structure assembled from complement components C5b through C9. The MAC embeds itself into the capillary walls, perforating the cell membranes and causing widespread destruction of the microvasculature.
This damage leads to a loss of capillaries and a subsequent lack of blood flow, or ischemia, to the surrounding muscle fibers. The resulting oxygen and nutrient deprivation causes the characteristic muscle fiber injury seen in DM, particularly the atrophy of fibers located at the edges of the muscle fascicles. This process is a form of self-inflicted vascular damage driven by the humoral branch of the immune system. The immune system’s misdirected attack on the muscle’s blood supply establishes the target that IVIG must neutralize to halt the disease progression.
Broad Mechanisms of Intravenous Immunoglobulin (IVIG)
IVIG contains polyclonal Immunoglobulin G (IgG) antibodies, representing the full spectrum of antibodies found in a healthy population. When administered in high doses, these pooled antibodies exert immunomodulatory effects on the recipient’s immune system.
One primary mechanism involves the saturation and blocking of Fc receptors (FcgRs) found on various immune cells, such as macrophages. The Fc region is the tail part of the antibody that immune cells use to recognize and bind to antibodies. By flooding the system with therapeutic IgG, IVIG occupies these receptors, effectively preventing the patient’s own pathogenic autoantibodies from binding and signaling the immune cells to launch an attack.
The infused antibodies also function as a decoy, neutralizing the harmful autoantibodies that drive the autoimmune response. The IgG molecules can bind directly to the circulating autoantibodies. This binding forms immune complexes that are then safely cleared from the bloodstream, reducing the concentration of the self-attacking antibodies.
Another element is that IVIG modulates the activity of lymphocytes, the specialized cells responsible for adaptive immunity. The treatment can suppress the proliferation and function of B-cells, which produce autoantibodies, and influence the balance of T-cells. It promotes the expansion of regulatory T-cells, which dampen excessive immune responses, and induces programmed cell death (apoptosis) in harmful, activated T-cells.
Targeted Effects of IVIG on Dermatomyositis Pathology
IVIG interrupts the complement cascade, directly addressing the formation of the Membrane Attack Complex (MAC) on the muscle capillary walls.
IVIG molecules, specifically the IgG antibodies, bind to and divert activated complement components, particularly C3b and C4b, which are crucial intermediate products in the cascade. By binding these fragments in the circulation, IVIG prevents their deposition onto the surface of the endothelial cells where they would otherwise assemble the MAC.
This interception is effective because the incorporation of C3b is a mandatory step for forming the C5 convertase, the enzyme complex necessary to produce the MAC. Interrupting this step prevents the subsequent assembly of the pore-forming C5b-9 complex. In clinical studies, muscle biopsies taken after IVIG treatment have shown a disappearance of C3b and MAC deposits from the endomysial capillaries, correlating with the patient’s clinical improvement.
By blocking this terminal pathway of complement activation, IVIG protects the existing capillaries from further lysis and allows for the restoration of the damaged microvasculature. The restoration of blood flow reduces muscle ischemia, leading to decreased inflammation and an improvement in muscle strength and overall physical function.
Administering IVIG Therapy
IVIG is administered as an infusion directly into a vein. The treatment regimen for dermatomyositis is typically an induction dose followed by monthly maintenance cycles. The initial dose is 2 grams per kilogram of the patient’s ideal body weight, delivered over two to five consecutive days.
Following the initial infusion, patients commonly receive a maintenance dosage, such as 1 gram per kilogram, every four weeks. The frequency and duration of therapy are individualized based on the patient’s response to treatment.
IVIG is utilized when initial immunosuppressive medications, such as corticosteroids, have not achieved sufficient disease control or when a patient experiences a severe, rapidly progressive form of DM. It is also sometimes used as a first-line treatment in acute, severe presentations to stabilize the patient quickly.