Autoimmune Disease

The complement system is traditionally considered as a defense limited to the recognition and elimination of foreign invaders (e.g. bacteria, viruses, and fungi) through direct cytolysis or stimulation of phagocytosis (innate responses). In recent studies, the versatile functions of complement system have extended to the initiation, regulation and effector mechanisms of innate and adaptive immunity. The contribution of complement to the surveillance of healthy and apoptotic/necrotic cells in our organism has been confirmed, pointing out the important role in the maintenance of homeostasis.

Multiple zymogens, receptors, and regulators form the complicated complement network, in which everyone is under the rigorous regulation to avoid excessive or insufficient activation. Once the delicate balance is broken, the complement system may cause extensive self-tissue inflammation. Dysregulation of the complement system has been involved in the pathogenesis and clinical symptoms of several autoimmune diseases, such as systemic lupus erythematosus (SLE), vasculitides, Sjögren's syndrome, antiphospholipid syndrome, systemic sclerosis, dermatomyositis, and rheumatoid arthritis.

Fig. 1 Illustration of autoimmune disease.¹

Pathophysiology of Autoimmune Diseases

Normally, the immune system can discriminate the foreign invaders and self-cells, while in an autoimmune disease, the immune system mistakenly attacks the healthy cells/tissue of our organism. There are many pathogenic factors of autoimmune disease.

1. The Appearance of Autoantigen: the release of sequestered antigen and the altered autoantigen.
2. Abnormal Immune Regulation: dysfunction of T helper cells (Th1, Th2).
3. The Existence of Cross-reacting Antigen.
4. Genetic and Environmental Irritants.

Fig 2. Autoimmunity is a result of a multi-orchestrated immune response. (Wang, et al. 2015)

Complement Associated Autoimmune Diseases

1. Complement Therapeutics for Systemic Lupus Erythematosus

Systemic lupus erythematosus (SLE) syndrome is a severe autoimmune disease characterized by fever, rash, glomerulonephritis and hemolytic anemia. SLE is often found to associate with a deficiency in complement C1q, C1r and C1s, moreover, C2 and C4 deficiency have a relationship with the development of SLE. In SLE patients, the complement system mediates target organ damage as well as in the effects on the development of autoimmunity in B and T cell lineages.

1. Hashimoto Disease

Hashimoto disease is an autoimmune disease in which the thyroid gland is gradually destroyed. The combination of genetic and environmental factors is thought to be the virulence factors. Complement participates in the pathogenesis owing to the binding to thyroid peroxidase antibody (TPOAb), subsequently mediate the cytolysis of thyroid follicular cells (TFC).

1. Systemic Sclerosis

Systemic sclerosis (SSc) is a connective tissue disease characterized by fibrosis of skin and internal organs, affecting the mobility of proximal extremities. In SSc patients, the complement C3d, C3d/C3, C4d, and C4d/C4 levels are higher than normal controls.

1. Complement Therapeutics for Rheumatoid Arthritis

Rheumatoid arthritis (RA) is an important human autoimmune disease, characterized by chronic inflammation of the synovium and subsequent destruction of cartilage and bone. Abundant evidence reveals that complement activation is involved in the pathogenesis of RA, especially C3, C5aR, CR2, and MAC.

Now the main therapeutic strategies for autoimmune diseases are inhibition of complement activation and complement receptors or membrane attack complex. Nonetheless, data from preclinical studies and initial clinical trials suggest that the modulation of the complement system has a potential therapeutical effect on the autoimmune conditions.

Creative Biolabs provides a series of therapeutic antibodies, inhibitors, soluble complement regulators, as well as customized services for complement-associated autoimmune diseases. Our comprehensive complement platform offers a great number of complement-related products in a rapid and cost-effective manner. If you are interested, please feel free to contact us for more details.

Reference
1. Glover, Katie, Deepakkumar Mishra, and Thakur Raghu Raj Singh. "Epidemiology of ocular manifestations in autoimmune disease." Frontiers in Immunology 12 (2021): 744396.
2. Wang, Lifeng, Fu‐Sheng Wang, and M. Eric Gershwin. "Human autoimmune diseases: a comprehensive update." Journal of internal medicine 278.4 (2015): 369-395.

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• Nephropathy
• Osteology
• Genetic Disease
• Infection
• Neurology
• Inflammatory Disease
• Ophthalmology
• Cardiovascular Disease
• Systemic Lupus Erythematosus-like Syndrome
• Hashimoto's Disease
• Systemic Sclerosis
• Rheumatoid Arthritis