Pediatric Complement Receptor Deficiency - An Overview

Introduction

The complement system plays an important role in an individual's immune system against various infections, inflammation, and defense against pathogens. Complement deficiency diseases manifest as infections caused by bacteria, recurrent angioedema, and inflammation involving the kidney and eyes. Pediatric complement receptor deficiency is an autoimmune complex disorder in which the complement system in children is dysregulated.

What is a Complement System?

The complement system is a cascade of multiple proteins which plays a major role in the host defense system. The complement system consists of various plasma proteins forming a cascade to help the host build an immune response against infections and inflammation. It also includes specific receptors for plasma proteins. These receptors are present in cells of the immune system.

What Is a Complement Receptor?

The complement receptor is the complement peptide that is present in cells. It is a multifunctional polymorphic glycoprotein on the plasma membrane of erythrocytes, eosinophils, B lymphocytes, and macrophages.

Following are the roles of complement receptors.

• It helps in the regulation of complement cascade pathways.

• It helps in the clearance of immune responses.

• It acts as a receptor for phagocytosis.

• It helps in the regulation of B-cells and T-cell responses.

• It is correlated with autoimmune disorders.

What Is the Function of a Complement System?

Following are the functions of the complement system.

• Defense against infectious agents.

• Act on the inflammatory response.

• It consists of plasma protein which acts as enzymes.

• It protects host cells from accidental complement attacks.

What Are the Biological Activities of Complement Systems?

Following are the three biological activities of the complement system.

• Opsonization-the phagocytes engulf the target, which is covered by plasma protein.

• It helps in the activation of leukocytes.

• It helps in the lysis of foreign bodies.

What Is Pediatric Complement Receptor Deficiency?

Pediatric autoimmune receptor deficiency is an autoimmune disease characterized by forming autoantibodies against multiple organs. It is a chronic disease. There is the formation of antinuclear antibodies. It is a rare heterogeneous disorder more commonly seen in females. This can be very severe and cause multiple complications. The disease is prepubertal in onset. Multiple organ damage occurs with advances with increasing age. Gene composition and ethnicity play a major role in the prevalence of this disease.

What are the causes of Pediatric Complement Receptor Deficiency?

The etiology of pediatric complement receptor deficiency is multifactorial. It involves genetic factors, environmental factors, and epigenetic mechanisms.

• Genetic Factor-There is an increase in the risk of this disease in monozygotic twins. It is a polygenic disease. It is caused by a mutation of the gene involved in the complement factor; if family members suffer from this disease, their genetic predisposition to the disease increases.

• Environmental Factors - These are also responsible for the development and manifestation of this disease. Ultraviolet light infections and toxins are responsible for the onset of this disease. This factor acts as the trigger which alters the DNA constituent. Prolonged exposure to ultraviolet light can lead to an increase in the amount of self-antigen-destroying dermal cells.

• Epstein Barr Virus - Epstein Barr Virus also acts as an inducer and proposer of this disease. This virus is responsible for marked B cell activation, producing many autoantibodies. This autoantibody leads to dysregulation of both innate and adaptive immune systems. It forms an immune complex that is associated with tissue damage.

What Is the Clinical Presentation Of Pediatric Complement Receptor Deficiency?

The child shows symptoms between one month to three years. During the onset of the disease, various symptoms such as fever, weight loss, arthralgia, arthritis, and renal disease are seen.

Following are the various symptoms seen in patients:

Constitutional Symptoms:

These are the most frequent symptoms seen in the child.

• Fever.

• Arthritis.

• Haematologic anemia.

• Renal nephritis.

• Cardiopulmonary disease.

• Gastrointestinal diseases.

Mucocutaneous Symptoms:

• Malar rash on the skin.

• Oral and nasal ulcers.

• Nonscarring alopecia.

Hematological Abnormalities:

• Leukopenia.

• Thrombocytopenia.

• Hematologic anemia.

• Secondary hemophagocytosis.

• Coagulation disorder.

Renal Abnormalities:

• Membranous nephritis.

• Sclerosing nephritis.

CardiopulmonaryAbnormalities:

• Chest pain.

• Pericarditis.

• Hemoptysis.

• Dyspnea.

• Inflammatory endocarditis.

• Myocarditis.

Neurologic Abnormalities:

• Headache.

• Mood disorder.

• Seizures.

• Psychosis.

• Cerebrovascular diseases.

• Chorea.

Gastrointestinal Abnormalities:

• Abdominal pain.

• Anorexia.

• Nausea.

• Vomiting.

• Bowel vasculitis.

• Autoimmune pancreatitis.

How to Diagnose Pediatric Complement Receptor Deficiency?

The diagnosis of the disease is confirmed by clinical examination of symptoms and laboratory investigation. Various biomarkers are investigated, such as serum C1q, urinary neutrophil gelatinase-associated lipocalin, and adiponectin. Anti Ribosomal antibodies, anti-neuronal antibodies, and plasma levels of NPR2A/B are evaluated.

What Is the Treatment of Pediatric Complement Receptor Deficiency?

A multidisciplinary approach is required for proper management. Pediatrician nephrologists and psychologists are needed for the proper treatment. The goal of the treatment is avoidance of inflammation, damage prevention, and minimizing the effects of medications.

Following are the various treatment options:

• Immunosuppressive Medications - Systemic glucocorticoids are used for treatment purposes. Cyclophosphamide is used for the management of severe organ failure. Mycophenolate mofetil has a cytostatic effect on B and T lymphocytes. Azathioprine is also used for gastrointestinal complaints.
• Biologic Agents - Various biological agents target pathways involved. Belimumab binds with B lymphocytes and stimulates protein-inhibiting biological activity. Rituximab is an anti-CD20 monoclonal antibody that targets B cells and their ability to produce antibodies.
• Hydroxychloroquine - It is an antimalarial agent given to patients as first-line therapy. It helps in decreasing morbidity and mortality. It helps in decreasing disease activity and flares.
• Vaccination - Due to the immunosuppressed and immunocompromised state of the children, there is a higher risk of bacterial fungal and viral infections. The administration of vaccines can reduce risks before initiating immunosuppressive therapies.

Conclusion

Production of autoantibodies, fluctuating disease, and immune complex deposition are seen in pediatric complement receptor deficiency. It leads to multiple organ damage. Due to dysregulation of the immune system seen in the pediatric population, children are affected by the various complications of this disease. It is very important for parents and pediatricians to rule out dysregulation of the immune system and decreased levels of the complement system of this disease due to the prevalence of this disease in the pediatric population.