Combined Immunodeficiencies

So my friends in our last posts we talked about B and T cell deficiencies independently, but what will happen if we put them into a blender and mixed it: 

Well yes, we will have the combined (mixed) immunodeficiencies. And depending on the recipe, some people can put more B or T cells, we will end with: Severe combined immunodeficiency, Wiskott-Aldrich syndrome and ataxia telangiectasia.

1) SCID:  (a.k.a. alymphocyotosis)

In the first disorder, what if we used all our B and T cells in the mixture, well we will have a complete absence of the immune system right? so this will be SEVERE and COMBINED (B and T cells), being also the most SEVERE of the primary immunodeficiencies. Even inside this SCID we will find several types, being the X linked the most common, followed by Adenosine deaminase deficiency (ADA deficiency)

This patients present with highly increased risk of developing infections, and because of their susceptibility they are also called "bubble boys" 

Which infections can they have? Severe bacterial, viral, or fungal infections early in life and often present with interstitial lung disease, chronic diarrhea, and failure to thrive. Also they can present with ear infections, recurrent PCP, and oral candidiasis. 

What findings we can expect? a small or even absence of thymic tissue, and absence of lymphoid tissue. Remember no B or T cells. So this also correlates with the lab findings where we will have decrease lymphocytes, decrease or absent immunoglobulins and lack of antibodies production after receiving vaccines.

What's the treatment?  The most common treatment bone marrow transplantation (BMT), which has been successful using either a matched related or unrelated donor, or a half-matched donor, who would be either parent. This has to start early in life because patients without treatment usually die before 1 year old due to recurrent infections.

2) WAS: Wiskott-Aldrich Syndrome

In this mixture we won't use all our T cells so they will be low but not absent, and same with B cells, will be decreased but not absent. What is characteristic in this syndrome is:

T: thrombocytopenia

I: immune deficiency

E: eczema

So this patients will present early in life with petechiae and easy bruising due to thrombocytopenia, (which can also lead to bloody diarrhea), then during the first month they present eczema, and then by 3 months presents recurrent infections. 

 

What is characteristic in the lab findings? think about the name...Wiskott...this W looks like an M right? just inverted. That's the clue, in this disorder they will have decrease IgM (W), on the other hand the vowels (A and E) will be elevAtEd...you see elevAtEd: IgA and IgE: and IgG can be either elevated, normal or lower.

How can me treat it? First avoid anything that interferes with platelets function (aspirin and other non-steroidal anti-inflammatory drugs. If severe low platelet counts is present, they might require platelet transfusions or a splenectomy. If frequent infections are present, intravenous immunoglobulins (IVIG) can be given (monthly). As a current cure we have hematopoietic stem cell transplant, accomplished through a cord blood or bone marrow transplant.

3) Ataxia-telangiectasia (a.k.a. Louis–Bar syndrome)

In this case this mixture will be similar as WAS, low but not absent B and T cells. So then how can we recognized it? Read the name again: Ataxia: lack of voluntary coordination of muscle movements, and Telangiectasia: small dilated blood vessels. Also presenting the immune deficiency, and a increase risk of develop cancer due to impaired DNA repair.

The ataxia will be progressive, starting when the child is learning to walk, showing some clumsiness. Also because of the cerebellar involvement they can present with oculomotor apraxia (lack of coordination between head and eye movements). Also present with increased risk of developing lymphomas and leukemias. 

How can we diagnose it? we have some lab tests that can help. The immunoglobulins will be decrease, especially IgA, also elevated and slowly increasing AFP after 2 years of age, chromosomal instability, increased sensitivity of cells to x-ray exposure and in imaging we can find cerebellar atrophy (MRI)

How can we treat it? For the ataxia part, we can handle it (not reverse it) with physical therapy, being this just symptomatic and supportive. To treat the immune deficiency we can give IVIG (be careful if its a selective IgA deficiency!!!), and having as current cure the bone marrow transplant.

So in summary

1) SCID: is severe and combined (both B and T cells), remember types, X linked the most common and ADA deficiency in second place, remember lab: lymphopenia, no response after vaccines. Treatment: BMT

2) WAS: remember TIE (thrombocytopenia, immune deficiency and eczema), invert the W and you have the M which is the deficient Ig in this disorder, remember which ones are elevAtEd (Ig A and E). Treatment: IVIG and BMT.

3) A-T: remember the component: ataxia and telangiectasia. Increase risk of lymphoma. Low IgA, increase AFP, cerebellar atrophy on MRI. Treatment: IVIG (not if complete IgA deficiency) and BMT.

I hope you enjoy this post,

For the next post I'll be explaining ocular problems in children.

See you on the next post,

Carlos Albrecht