I have a 45 y/o female with recurrent sinus infections and four hospitalizations for pneumonia in the last 8 years. Each episode progressively getting worse. Most recent one requiring admission to ICU and was subjected to intensive infectious disease workup. She has no GI problems and no diagnosed autoimmune conditions. She does have significant seasonal allergies

Immune work up shows IgA 47 (n 81 - 463), IgG 615 (n 694 - 1618), IgM <5 (N 48 - 271), Low IgG2 at 142 (N 241 - 700)

Antibody titres to Tetenus Normal, antibody titres to S pneum protective range for 15/23 serotypes.

Mitogen stimulation to PHA, CON A, PWM normal. Lymphocyte Antigen Screen stimulation indices for Tetenus, Candida and PPD normal.

Lymphocyte subset panel all indices in normal range.

Immune assessments of B cell subsets (Mayo clinic) shows: CD19 normal at 11% , CD27 4% (N 6.3 - 52.8%), CD27+ IgM- IgD- low at 1.5% (N 2.3 - 28%), CD 27+ IgM+ IgD- only 0.3% (N 0.0 - 5.3%), IgM+ % of CD19+ B cells high at 82.7% (N 26.0 - 78.0%), CD21+ 98.7% of CD19 B cells, CD21- % of CD19+ B cells at 1.3% all the other indices from Immune assessment of B cells are normal.

To me it appears that she fits into MB0 category of Paris classification and for the Euro classification group B+ smB- with CD21,norm.

I have two questions:
1. should we get genetic studies ?

2. Would she benefit from Immunoglobulin replacement therapy even though her antibody titers to Tetenus and S. pneum and all the stimulation indices are normal and her IgG is really not very low although she has low IgA and her IgM level is below the detectable level for the lab? Thanks.


Thank you for your inquiry.

I am sending your question to Dr. Charlotte Cunningham-Rundles, who is an internationally recognized expert in immune deficiency disorders, especially common variable immunodeficiency. When we receive Dr. Cunningham-Rundles’ response, I will forward it to you.

Thank you again for your inquiry.

Phil Lieberman, M.D.

We received a response from Dr. Cunningham-Rundles regarding your Ask the Expert inquiry. Thank you again for your inquiry and we hope this response is helpful to you.

Phil Lieberman, M.D.

Response from Dr. Charlotte Cunningham-Rundles:

As this woman has a nearly normal IgG and antibody to both protein and a number of pneumococcal serotypes, she does not have CVID and so the Paris classification for CVID is not pertinent. (This classification is only for those who completely qualify for this diagnosis and has no relevance for anyone else.) I would not suggest genetic tests here as none are pertinent to her situation.

(Also, the Mayo ranges for these values do not appear to be similar to any published ranges for normal adults and thus are not very helpful here.)

She does have a low or absent serum IgM and that is curious and might be important with regard to her medical history, which is otherwise not well explained. (Was this repeated to verify?) Immunologists do not have good antibody data about subjects with absent IgM as our tests only measure IgG, but in theory, she may not be well equipped to deal with new infections. One could test isohemagglutinins, if she is blood group A or B or O as these antibodies are mostly IgM.

She may need prophylactic antibiotics, or perhaps Ig replacement, if the evidence for bacterial infections is strong.

Best regards,
Charlotte Cunningham-Rundles

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