C3 Deficiency, Complement Deficiencies

Genetically determined C3 deficiency in Brittany spaniel dogs shares a number of biochemical and clinical characteristics with the human disorder.² Like their human counterparts, dogs with a genetically determined complete deficiency of C3 also develop renal disease. Some patients also develop transient erythematous rashes in association with pus-forming infections. The C3-deficient dogs develop significant bacterial infections, such as pneumonia, sepsis, and pyometra, which are caused by Clostridium spp., Escherichia coli, and Klebsiella spp. C3-deficient dogs who have significant infections also may subsequently develop renal disease.³

Dogs with c3 deficiency also commonly develop kidney disease, characterised by excessive thirst and urination, weight loss, loss of appetite, mouth ulcers and depression. In some cases the kidney disease may progress to kidney failure and death.

Immunodeficiency disorders involve malfunction of the immune system, resulting in infections that develop and recur more frequently, are more severe, and last longer than usual. Immunodeficiency disorders impair the immune system's ability to defend the body against foreign or abnormal cells that invade or attack it (such as bacteria, viruses, fungi, and cancer cells). As a result, unusual bacterial, viral, or fungal infections and rare cancers may develop.¹

Complement is the term used to describe a group of blood serum proteins that are critically important in our defense against infection. The complement system includes at least 30 proteins. The first nine of these proteins were given numbers as their names, such as C1, C2, C3, etc. As more proteins were discovered they were named with letters, such as Factor B and Factor D. Still, others were given more descriptive names such as C1 Inhibitor.

These proteins act together to provide critical help in our defense against infection in a number of ways. One of the proteins, C3, acts to coat bacteria so that the bacteria are more easily ingested, or eaten, by white blood cells. Others, C3, C3, C7, C8 and C9, assemble on the surface of a certain kind of bacteria and punch holes in the bacteria, causing them to rupture and die. Finally, small fragments of two of the complement proteins, C3 and C5, can cause an increase in blood supply and the attraction of white blood cells to local areas of infection, both of which are needed to clear an infection.

There are deficiencies in each of the individual components of complement. For example, there are individuals deficient in C2, individuals deficient in C3, individuals deficient in C5, individuals deficient in C1 Inhibitor, etc.

Deficiencies of the Third Component of Complement (C3) and those proteins of the complement system that activate C3

The third component of complement (C3) is the protein that coats bacteria and makes them more susceptible to being eaten by a certain kind of white blood cell, phagocytic. Patients who are deficient in C3 or the proteins that are necessary to activate C3 (e.g. C1, C2 and C4).

are susceptible to a variety of bacterial infections. Although patients with deficiencies of C3, C1 or C4 are quite rare, patients with deficiencies of C2 are more common, occurring as frequently as 1 in 10,000 in the general population.

Diagnosis of C3 Deficiency

A variety of laboratory tests are used to diagnose patients with deficiencies of individual complement proteins or components.

Most of the complement proteins and regulators are inherited as autosomal recessive genes; this means that there are two copies of each gene present, one contributed by each parent. There are two exceptions: 1. A deficiency of properdin, is inherited as an X-linked recessive trait 2) C1 Inhibitor Deficiency (or Hereditary Angioedema) requires the presence of only one abnormal gene out of the two genes for this protein to produce the disease.

Treatment of C3 Deficiency

At this time, it is not possible to replace the missing components of the complement system. In general, these proteins have rapid turnover and often must be made by the body on a daily basis. Therefore, long-term replacement therapy is not an option since injections of highly purified components would be required almost every day and the proteins are difficult to purify. Patients with abnormalities that are associated with a high frequency of infection are usually helped by immunization when available and, occasionally, are treated with prophylactic antibiotics.

Prognosis for C3 Deficiency

Most patients with complement deficiencies can expect to become productive adults if they are recognized as having the deficiency and treated early and vigorously.

References

1. IDF Patient & Family Handbook For Primary Immunodeficiency Diseases, 4th Edition
2. Johnson JP, McLean RH, Cork LC, Winkelstein JA. Genetic analysis of an inherited deficiency of the third component of complement in Brittany spaniel dogs. Am J Med Genet. 1986 Nov;25(3):557-62.
3. Joanne R. Blum b, c, d, a, Linda C. Cork b, c, d, a, Jeanette M. Morris b, c, d, a, Jean L. Olson b, c, d, a and Jerry A. Winkelstein. The clinical manifestations of a genetically determined deficiency of the third component of complement in the dog.