two girls on a hospital bed

Immunohematology and Immune Dysregulation

What We Treat

At the Aflac Cancer and Blood Disorders Center of Children’s Healthcare of Atlanta, one of our missions is to provide a medical home for children with complex, multisystem autoimmune disorders that arise from an underlying defect in immune regulatory pathways. The Immunohematology and Immune Dysregulation Program offers focused immune and genetic evaluation of patients with either early onset or refractory autoimmune conditions with the goal of providing targeted immune modulatory and biological therapies based on immune profiles and genetics.

Patients with underlying monogenetic immunohematology and immune dysregulation disorders are treated through different subspecialties because many will have more than one autoimmune manifestation and may not respond to conventional management. Identifying underlying immune and genetic etiologies is critical to the effective long-term management of these disorders.

Our program evaluates and treats the following group of patients:

Autoimmune lymphoproliferative syndrome (ALPS) and ALPS-like conditions

Autoimmune cytopenia with or without lymphoproliferation is not uncommon in hematology practice. In general, autoimmune cytopenia with lymphoproliferation is evaluated for classical ALPS. However, in several of these patients, the work-up for classical ALPS is negative. Increasingly, autoimmune cytopenias and lymphoproliferation are recognized as one of the typical presentations of underlying immune regulatory disorders. These patients are usually referred to as "ALPS-like" and novel genetic defects (i.e. mutations in STAT3, CTLA-4, LRBA, PIK3CD) have been identified in this cohort of patients. Through targeted immune and genetic testing, we are able to identify the immune and genetic abnormality in many of these patients and offer appropriate therapeutic interventions, includingsirolimus, abatacept, tocilizumab and ruxolitinib.

Immune dysregulation-polyendocrinopathy-enteropathy, X-linked (IPEX) and IPEX-like

IPEX is a genetic disorder that impairs function of a type of white blood cell that regulates the immune system. Without an effective regulatory mechanism, there is decreased tolerance to self, resulting in the immune system attacking one’s own body. It can cause difficult to treat inflammatory bowel disease (IBD), resulting in diarrhea and failure to thrive, severe eczema and auto-immune endocrinopathies such as Type 1 diabetes. IPEX is due to a defect in the FOXP3 gene. However, several other defects that affect T cell tolerance, activation and proliferation result in similar clinical symptoms; they are commonly referred to as IPEX-like conditions.

Common variable immune deficiency (CVID)

CVID is associated with low immunoglobulin levels that can lead to recurrent sinus and lung infections. A significant proportion of these patients also have autoimmunity and lymphoproliferation, as well as varying degrees of T cell defects, which are best characterized as late onset combined immune defect.

Very early onset inflammatory bowel disease (IBD) and treatment refractory IBD

IBD is identified as a presenting manifestation or primary immune defect. A high percentage of patients presenting with IBD younger than 5 years old or treatment refractory IBD will have an underlying immune and genetic defect.

Periodic fever syndromes and autoinflammatory syndromes

Patients presenting with unexplained recurrent fevers without an obvious infectious cause might need evaluation for underlying periodic fever syndrome and autoinflammatory syndromes.

Hemophagocytic lymphohistiocytosis (HLH)

​HLH is a hyperinflammatory disorder that can be rapidly fatal if not recognized and treated early. Defects in T and NK cell cytotoxicity lead to primary HLH. However, patients with an overwhelming infection, such as Epstein-Barr virus, underlying malignancy and systemic rheumatological conditions, could also have HLH. Comprehensive evaluations are performed to identify underlying causes, and effective management is ensured through a dedicated team of physicians with expertise in clinical management and research in HLH.

In addition to focusing on the evaluation of immune dysregulation disorders, the clinic offers referral to hematopoietic stem cell transplant (HSCT) for patients with classic immune defects and immune dysregulation disorders.

We may be able to help your child if he or she has any of the following clinical problems:

  • Immune cytopenia with autoimmune hemolytic anemia (AIHA) and/or immune thrombocytopenic purpura (ITP) with other autoimmune manifestations
  • Immune cytopenia with hypogammaglobulinemia, enlarged lymph nodes, or spleen enlargement
  • Persistent hypogammaglobulinemia following Rituximab treatment
  • Recurrent fever without an obvious infectious cause
  • Diagnosis of IBD at younger than 5 years old
    • IBD refractory to first and second line medical treatments
    • IBD associated with other autoimmune manifestations such as immune cytopenias, or low blood counts, and autoimmune endocrinopathy
    • IBD with a course complicated by difficult-to-treat fistulating disease
  • Refractory rheumatologic condition
  • Lupus with age of onset younger than 5 years old
  • Early onset or difficult-to-manage systemic idiopathic arthritis
  • Hemophagocytic lymphohistiocytosis
  • Recurrent macrophage activation syndrome
  • EBV-driven hemophagocytic lymphohistiocytosis

Our Unique Approach

The Immunohematology and Immune Dysregulation Program provides comprehensive immune system and genetic evaluations that lead to targeted and individualized therapies. Our team works closely with other specialties, including rheumatology, GI services and hematology/oncology, to complement care and assist in genetic diagnosis and treatment options.

Our highlights

  • Our active research helps us better understand and treat immune dysregulation disorders.
  • We have haplo-identical transplant protocols in place for patients with limited or no unrelated donor options.
  • We manage the largest pediatric hematology program in the country, caring for more than 3,000 patients each year.
  • We performed 88 BMTs in 2018, and more than 1,000 since our program began in 1985.
  • We have 100-plus-day survival rates—better than the national average for autologous and allogeneic transplants.

Services We Offer

We provide consultation for HSCT for children whose diagnosis suggests that transplant might be an option for curative treatment. Shanmuganathan Chandrakasan, MD, has expertise in the management of immune deficiency and dysregulation disorders, and in hematopoietic stem cell transplant. To achieve excellent HSCT outcomes, the team invests a considerable amount of time and effort in optimizing medical management of immune deficiency and dysregulation disorders prior to HSCT. Comprehensive management of care is provided through each stage, from diagnostic testing to the transplant process and post-transplant follow-up.

We provide:

  • Immune and genetic evaluation for immunohematology and immune dysregulation disorders
  • Genetic counseling
  • Targeted and biological therapies based on immune and genetic abnormalities
  • HSCT for immune defects

Call 404-785-1200 or have your primary care physician make a referral if you would like to have your child evaluated in the Immunohematology and Immune Dysregulation Clinic.

Learn more about our BMT program

Meet the Team

Our immune dysregulation team