A quick summary of primary immunodeficiencies

Antibody

When people talk about immunodeficiency states, they’re usually talking about secondary immunodeficiencies, like AIDS.

The primary immune deficiencies really don’t get much press. Which is unfortunate, because although they are much less common than secondary immune deficiencies, they still occur, and it’s important to understand them for that reason alone. Plus, they are very testable – either on board exams, or on class exams.

Time is short, though, and you need to know the basic points for each one without having to wade through a lot of chapters in a textbook. So, without further ado, here is a short, bullet-pointed list of the main disorders, with particular emphasis on the part of the immune system that is affected, and the clinical manifestations of the disease.

X-linked agammaglobulinemia

  • Pre-B cells can’t differentiate into B cells
  • Patients have no immunoglobulin (Ig)
  • X-linked (so seen only in males)
  • Presents at 6 months of age (when maternal Ig runs out)
  • Patients get recurrent bacterial infections
  • Treatment: intravenous pooled human Ig

Common variable immunodeficiency

  • Group of disorders characterized by defective antibody production
  • Affects males and females equally
  • Presents in teens or twenties
  • Basis of Ig deficiency is variable (hence the name) and often unknown
  • Patients more susceptible to infections, but also to autoimmune disorders and lymphoma!

Isolated IgA deficiency

  • Most common of all primary immune deficiencies
  • Cause is unknown
  • Most patients asymptomatic
  • Some patients get recurrent sinus/lung infections or diarrhea (IgA is the major Ig in mucosal secretions)
  • Possible anaphylaxis following blood transfusion (patients have anti-IgA antibodies, and there is IgA in transfused blood!)
  • Increased incidence of autoimmune disease (who knows why)

Hyper-IgM syndrome

  • Patients make normal (or even increased) amounts of IgM
  • But can’t make IgG, IgA, or IgE!
  • X-linked in most cases
  • Patients also have a defect in cell-mediated immunity
  • Patients have recurrent bacterial infections and infections with intracellular pathogens (e.g., Pneumocystis jiroveci)

DiGeorge syndrome

  • Developmental malformation affecting 3rd and 4th pharyngeal pouches
  • Thymus doesn’t develop well
  • Patients don’t have enough T cells
  • Infections: viral, fungal, intracellular pathogens
  • Patients may also have parathyroid hypoplasia
  • Treatment: thymus transplant!

Severe combined immunodeficiency

  • Group of syndromes with both humoral and cell-mediated immune defects
  • Patients get all kinds of infections
  • Lots of very different genetic defects
  • Half of cases are X-linked
  • Treatment: bone marrow transplantation

The best way to remember these might be to make a little chart, with the diseases in one column, and subsequent columns for transmission (X-linked or not), immunologic defect (e.g., no immunoglobulin production), and clinical features (e.g., infant with recurrent bacterial infections).

What’s the Kleihauer-Betke test used for?

syringe

If you read this post about hemolytic disease of the newborn, you already know the answer: it’s used for determining the amount of fetal blood that has backed up into the mom’s circulation.

It’s usually done for the purpose of determining Rhogam dose. You need to make sure you give enough Rhogam to suppress the mom’s immune response. If there has been a little bleed, you give a little; if there has been a big bleed, you need to give more. Take a look at this chart if you want to know exact doses.

Here’s how it’s done:

1. Prepare blood smear from mom’s blood.

2. Expose blood smear to acid bath (this removes adult hemoglobin, which is acid-sensitive) but not fetal hemoglobin.

3. Stain smear. Fetal cells appear dark pink; maternal cells look like “ghosts.” Here’s what this looks like:

4. Count lots of cells and report percentage of cells that are fetal (specifically: you count the number of fetal blood cells per 50 low power fields. If you see 5 cells per 50 low power fields, that’s equivalent to a 0.5 mL fetomaternal hemorrhage).

If you want to get really fancy, you can look for fetal blood cells using flow cytometry. Using a sample of mom’s blood, apply an anti-HbF (fetal hemoglobin) antibody, and then run the sample through the flow cytometer. In the little printout, look for cells that stain intensely with HbF: these are baby’s cells! A few of mom’s cells will have weak HbF staining – this is normal in adults.

Top image credit: adamr.stone (http://www.flickr.com/photos/adamrstone/3098924060/) via cc license.

Hemolytic disease of the newborn

Phototherapy

Hemolytic disease of the newborn (HDN) is a disease in which there is hemolysis in a newborn or fetus caused by blood-group incompatibility between mother and child. (more…)

Real examples of hypersensitivity reactions

canola fields

Sometimes we (okay, I) get so caught up in describing pathologic mechanisms that real-life examples get the short end of the stick. Let’s look at some real diseases in which the underlying problem is a hypersensitivity reaction. (more…)