HomeHealth articlesalloimmune neonatal neutropeniaWhat Is Alloimmune Neonatal Neutropenia?

Alloimmune Neonatal Neutropenia - Possible Causes, Diagnosis and More

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Alloimmune neonatal neutropenia occurs in mothers having antibodies against human neutrophil antigens.

Medically reviewed by

Dr. Faisal Abdul Karim Malim

Published At January 31, 2023
Reviewed AtJanuary 31, 2023

Introduction

Blood contains the fluid part, plasma, and cells. The cells include red blood cells, white blood cells, and platelets. The white blood cells are divided into granulocytes and agranulocytes based on the presence of granules inside the cells. Granulocytes include neutrophils, eosinophils, and basophils. Neutrophils are the cells that are the first line of defense against infection. If the number of neutrophils is lesser, the condition is called neutropenia. This condition poses a high risk for infection.

What Is Alloimmunity?

Alloimmunity is the type of immunity where an immune response is produced against antigens from members of the same species. For example, transplanted tissue undergoing graft rejection. It occurs when the major histocompatibility complex (MHC) genes of the donor and recipient are different. The T cells and B cells are involved in the process. The T cells cause cellular rejection, whereas the B cells are involved in humoral rejection leading to the production of antibodies against the donor’s major histocompatibility complex molecules.

What Is the Difference Between Alloimmunity and Autoimmunity?

Autoimmunity is different from alloimmunity, which produces an immune response against one's own body tissues, cells, and cellular components. The immune responses are usually triggered in response to a pathogen or an antigen. When these immune responses are directed against the cells and tissues of the body, they may lead to autoimmune diseases such as rheumatoid arthritis, Grave’s disease, etc.

What Are Neutrophil Antigens?

Human neutrophil antigens are proteins present on the surface of neutrophils, similar to blood group antigens expressed on the surface of red blood cells. They have a significant role in alloimmunity and autoimmunity.

How Are Human Neutrophil Antigens Inherited?

The baby inherits human neutrophil antigens from both parents. So, for example, suppose the mother shows human neutrophil antigens - 1b on her neutrophils and the father has human neutrophil antigens - 1a on his cells, and the baby’s neutrophils have both human neutrophil antigens - 1b and 1a.

What Are Antibodies?

The antibodies, also called immunoglobulins, are proteins that identify and neutralize the foreign substances in the body, such as bacteria and viruses. In addition, they recognize the unique particles in the foreign substance called the antigens and fight the disease-causing organism or the foreign cell with antigen.

What Is Alloimmune Neonatal Neutropenia?

Alloimmune neonatal neutropenia is a condition characterized by a reduction in the number of neutrophils in the neonate due to the production of antibodies by the mother against the human neutrophil antigens. These antibodies cross the placenta and destroy the baby’s neutrophils. The risk is not noticed when the mother stays healthy, and the baby is in the womb. But there is a great risk of decreased neutrophil count once the baby is born.

What Does It Mean if the Mother Has Neutrophil Antibodies?

The presence of neutrophil antibodies in the mother will not affect the normal life of the mother. Still, there is a risk of the child getting affected by the antibodies leading to neutropenia. The risk can be assessed by collecting blood samples from the father.

Can a Person With Neutrophil Antibodies Donate Blood?

A person with neutrophil antibodies is not eligible to donate blood as they tend to destroy the neutrophils of the recipient. When you get checked, the doctor issues a report that states neutrophil antibodies in your blood must be carried out anytime you reach a hospital for treatment.

What Are the Possible Causes of Neonatal Neutropenia?

  • Alloimmune neonatal neutropenia due to maternal alloantibodies.

  • Autoimmune neutropenia of infancy.

  • Maternal drugs.

  • Pregnancy-induced maternal hypertension.

  • Hemolytic disease of the fetus and newborn.

  • Neonatal infection.

  • Congenital virus infections.

  • Twin - twin transfusion.

What Are the Symptoms of Alloimmune Neonatal Neutropenia?

There is a decrease in the absolute neutrophil count in the baby during birth. The number decreases further in the first week and can last for around six months. In some cases, no clinical signs of infection are noticed due to neonatal neutropenia. But in other cases, symptoms such as fever, omphalitis (infection of the umbilicus and surrounding tissues), pneumonia, meningitis, and sepsis may be encountered. The neonatal neutropenia causing fulminant infections can be fatal at times.

How to Diagnose Alloimmune Neonatal Neutropenia?

  • Neutrophil Concentration: The neutrophil count in neonates varies significantly in the first week. The count can depend on the child's birth weight, age, and race. The average neutrophil count in a baby with a birth weight less than 1500 grams is around 500 per microliter, and the count for a baby with a birth weight greater than 1500 grams is between 2000 to 14500 per microliter. If no underlying cause is identified, further evaluation is done to determine the treatment.

  • Bone Marrow Examination: When there is no clue of the cause through blood examination, a bone marrow examination is conducted to detect if the baby has congenital neutropenia.

  • Antibody Detection: Serological examination is performed for suspected cases of alloimmune neonatal neutropenia. Human neutrophil antigen typing is carried out for both parents and neonates. And a crossmatch of maternal serum with paternal granulocyte is recommended.

  • Antigen Specificity: Monoclonal antibody immobilization of granulocyte antigens is an assay performed to confirm human neutrophil antigen specificity.

  • Antigen Typing: The human antisera can be used for antigen typing.

  • Genotyping: It can be used to predict human neutrophil antigen phenotype.

How to Treat Alloimmune Neonatal Neutropenia?

In severe cases of neutropenia, therapeutic and prophylactic antibiotics are recommended. In addition, for children suffering from severe infections due to neutropenia, a granulocyte colony-stimulating factor can be used to elevate the levels of neutrophils. The intravenous infusion of immunoglobulins can also be used as a second line of treatment. Other treatments may include steroids, exchange transfusion, leukocyte transfusion, etc.

Conclusion

Although alloimmune neonatal neutropenia is rare, the newborn can be seriously affected if diagnosed later and can lead to life-threatening complications. Therefore, the diagnosis of the disease should be made at the earliest with the necessary investigations, and in most cases, treatment with an antibiotic is found to be effective.

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Dr. Faisal Abdul Karim Malim
Dr. Faisal Abdul Karim Malim

Pediatrics

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