Common Variable Immunodeficiency: Not That Common

This is really only my first post on here, the other posts being reposts of answers to questions on the PiA Discussions Forum (if you have a primary immune problem and haven't yet done so, take a few moments to visit and introduce yourself!).

So I thought it appropriate that my first post be about my diagnosis: common variable immunodeficiency, or CVID as it's most commonly known. The first thing I'd like to stress is that CVID isn't common in terms of incidence: that is to say it's quite a rare disorder.

What is CVID?

In fact it's not even 'a' disorder: it's a big old collection of about 20-30 disorders which have shared features and treatment plans. That's where the "common" bit comes in: there are common variances in the immune systems of us with CVID.

In other words, CVID is what I term a bucket diagnosis. Bucket diagnoses are useful when they are used appropriately as they allow appropriate treatment and monitoring whilst discovering the underlying problems.

So what are those common variances? Patients with CVID always have low IgG levels, and normally have low IgA and may also have low IgM levels (for more details on immunoglobulins, see my post, Immunoglobulins: proteins that play tag). Functional antibody (FAb) tests typically reveal that antibodies produced are effective, but may reveal that antibodies against certain types of pathogens aren't produced (for example, my body is quite happy fighting Clostridium tetani (tetanus), but doesn't like Pneumococcus sp. in the slightest). CVID patients typically have a normal white blood cell count (T and B cells); patients which do not typically have low B cell count and these patients typically have atypical X-linked agammaglobulinaemia.

A patient with CVID (or indeed many other PIDs) will typically have a history of

• Serious
• Persistent
• Unusual or
• Recurrent

infections. Typically, such infections in CVID patients tend to be bacterial in nature (for reasons which will hopefully become apparent), and the most commonly reported infections are respiratory tract infections (sinusitis, tonsilitis, bronchitis, pneumonia) and digestive tract infections.

Chest infections can cause long-term damage to the lungs (most commonly bronchiectasis), whilst in children the digestive problems can cause "failure to thrive" because the prevent the child absorbing essential nutrients.

CVID affects about 1 in 10,000-50,000 people; the reason for this broad range is that many people are undiagnosed. This means that there are between 1,200 and 6,000 people with CVID in the UK, or between 6,000 and 32,000 in the United States of America. This represents about 50% of the cases of primary immunodeficiency (OK, you could argue that makes it common, but I'm so not common!).

So, What’s Broken?

We've established that CVID is characterised by low levels of antibody, but what causes CVID? That's a good question. It's highly likely to either be genetic or to have a strong genetic factor. First, let's have a quick look at the natural history of the antibody.

In the image to the right you can see that there are several cells involved before antibody production can occur.

The main cell is the B cell, which take samples of antigen and develop antibodies to it. T Helper 2 (TH2) cells verify that the antigen is foreign, and when they recognise an antibody for a pathogen which is active they stimulate the B cells to divide.

Most of the daughter B cells become plasma cells, which churn out thousands of antibodies. The remainder become B memory cells which hang around in lymphoid tissue (ie. in lymph nodes) waiting to be activated and produce antibody if reactivated.

You can see that there are lots of places at which this process could breakdown: TH2 to B cell signalling, B cell to TH2 presentation, B cell differentiation, antibody production or memory B cells reactivation.

So which breakdown in CVID? Uhm, well, probably all of them. CVID is a bucket diagnosis precisely because we don’t know what all of the problems are!

However, scientists recently identified some genetic mutations which appear to cause CVID, of which the most important is the TACI mutation, which responsible for about 10% of cases.

TACI (transmembrane activator and CAML interactor, well you did ask…) is a surface protein on B cells which facilitates switching between different isotypes (IgG, IgM, IgA are each isotypes) of immunoglobulin. TACI is also responsible for some selective IgA deficiency (SIgAD) cases, which explains at least one relationship between SIgAD evolving to CVID.

Other genetic mutations include BAFF-R (a defect on a B cell surface protein), ICOS (a defect on a TH cell surface protein) and CD19 defects (a B cell surface protein defect). Professor Grimbacher’s research at the Royal Free Hospital has indicated that there may be other links to T cell defects as a result of increased complications of Epstein Barr Virus infection in patients with CVID (although interestingly the actual infection rates in CVID patients mirror those of the general population, about 50%).

How Can We Fix It?

At the moment there are no permanent fixes, but we can treat the symptoms quite successfully.

The main treatment is the recognition and appropriate treatment of infection, particularly bacterial and protoctist (parasitic) infections. Typically, this involves a high-strength, extended course, broad spectrum antibiotic. If this doesn’t affect the infection, the doctor should prescribe a second course of a different antibiotic and order a culture of the appropriate bodily fluid (eg. throat swab, nasal mucus sample, faecal sample etc…). It is antibiotics that save lives in CVID; everything else is about quality of life.

Commonly, patients with CVID are given immunoglobulin infusions, a topic which warrants its own post. These “top up” the levels of antibody which are missing by using antibodies taken from blood donations. These help prevent infections, and also appear to control aches and pains which are common in CVID patients.

CVID patients should see their specialist at least once a year, get regular (eg. annual) lung function tests and abdominal ultrasound scans, with CT scans every few years. The appointment with the specialist should involve a full body examination; this is because some people with CVID are prone to higher rates of abnormal tissue growth which can lead to malignant growths if undetected.

Some patients with CVID also have autoimmune conditions (such as lupus or rheumatoid arthritis), and the various specialists should talk to each other to decide the best treatment protocols (typically, autoimmune disorders are treated using immune supressants which may cause issues in people with already poor immune systems!).

All that said, CVID patients without serious complications can expect a good quality of life and normal life expectancy.

That’s me done for tonight; I’m going to have a mix of longer posts and shorter posts, but for obvious reasons we seem to be starting with the longer ones…