Pediatric Complement Receptor Deficiency - An Overview

Introduction

The complement system plays an important role in an individual's immune system's defense against various infections, inflammation, and pathogens. Complement deficiency diseases manifest as infections caused by bacteria, recurrent angioedema, and kidney and eye inflammation. 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 that plays a major role in the host defense system. It comprises various plasma proteins forming a cascade to help the host build an immune response against infections and inflammation. The complement system also includes specific receptors for plasma proteins, which 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 regulate complement cascade pathways.

• It helps in the clearance of immune responses.

• It acts as a receptor for phagocytosis.

• It helps regulate B-cell and T-cell responses.

• It is correlated with autoimmune disorders.

What Is Complement Pathophysiology?

The system of plasma proteins is the complement, which can be directly activated by pathogens or indirectly by pathogen-bound antibodies. This can lead to a cascade of reactions on the surface of the pathogens and generate active components with various effector functions.

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 an enzyme.

• 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 plasma protein covers.

• 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 in 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: Monozygotic twins are at an increased risk of this 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 it increases.

• Environmental Factors: These are also responsible for developing and manifesting this disease. Ultraviolet light infections and toxins are responsible for the onset of this disease. This factor acts as the trigger, altering 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 induces and promotes this disease. This virus is responsible for marked B cell activation, producing many autoantibodies. These autoantibodies lead to dysregulation of both innate and adaptive immune systems. They form 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 and three years old. Various symptoms, such as fever, weight loss, arthralgia, arthritis, and renal disease, are seen at the onset of the disease. Following are the various symptoms seen in patients:

Constitutional Symptoms:

These are the most frequent symptoms seen in the child.

• Fever.

• Arthritis.

• Hematologic 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, such as serum C1q, urinary neutrophil gelatinase-associated lipocalin, and adiponectin, are investigated. Anti-ribosomal antibodies, anti-neuronal antibodies, and plasma levels of NPR2A/B are evaluated.

What Is the Treatment of Pediatric Complement Receptor Deficiency?

Proper management requires a multidisciplinary approach. Pediatricians, nephrologists, and psychologists are needed for proper treatment. The goal of treatment is to avoid inflammation, prevent damage, and minimize 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 the involved pathways. 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 decrease morbidity and mortality, disease activity, and flare-ups.

• Vaccination: Children with immunosuppression and immunocompromised states are at a higher risk of bacterial, fungal, and viral infections. Vaccines can reduce these 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. Parents and pediatricians need 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.