[CIS PIDD] [cis-pidd] MGUS with reduced serum IgM and IgG subclasses & recurrent infections
Stan Ress
stan.ress at uct.ac.za
Mon Dec 15 03:46:55 EST 2014
Dear Colleagues,
I've recently seen 2 patients with this problem, where the issue is how to distinguish between MGUS with immune paresis and late onset PID as the cause of reduced serum Ig and recurrent infections. I'd appreciate any advice on the patient below.
A 67 year-old lady has a background history of hereditary angioedema, allergic rhinitis and recurrent sinusitis. She underwent sinus surgery in 1999 with bilateral uncinectomies and splitting of left middle turbinate for a concha bullosa anomaly, and placement of a right grommet T tube. Thereafter, she has had recurrent sinus infections requiring multiple courses of antibiotics. She is known to have stable monoclonal peak of IgG kappa of 11 g/L for several years, with negative urine light chains. On 25 March 2014 total serum IgG was 18.4 g/L, her pulmonologist also documented serum IgG2 deficiency and a reduced serum IgM of 0.26 g/L and she was referred to me in April for evaluation of her immune status. However, the reduced IgG2 subclass is difficult to interpret and may be an analytical issue because at the same time total IgG subclasses added up to only 14.06, leaving a significant gap of 4.34 g/L. Although total serum IgG and IgG subclasses are both measured by nephelometry, they are measured on different platforms and differences in the values obtained is well documented.
Immune subsets determined by flow cytometry indicated reduced B-cell percentage (4%) and absolute count (95/uL). CD3+ (1630/uL) was normal range, while a low CD4+ subset (562/uL) and elevated CD8+ subset (948/uL) accounted for a low CD4/8 ratio of 0.59. NK subset was normal (322/uL). Within the B-cell population there was the following distribution of memory B-cell subsets:
* Naïve B-cells IgD+ CD27- (75%),
* Non-switched memory B-cells IgD+ CD27+ (7%),
* class-switched memory IgD- CD27+ (11.25%)
Baseline vaccination status on 8 April 2014 showed protective specific IgG antibody levels for Haemophilus B Influenza IgG - 1.92, (sufficient protection). However, Diptheria IgG -0.02, tetanus toxoid IgG - 0.02, Strep pneumonia IgG - 13.32 (> 35), and pertussis-5.23 were all suboptimal values. Following vaccination with Pneumovax 23 in May, there was a good response with a repeat Strep pneumonia IgG of >270, and also a response to Hiberix (tetanus conjugated Haemophilus B) vaccination with haemophilus B IgG of 3.07, but tetanus unchanged at 0.02. She then was vaccinated with Boostrix tetra (D. toxoid, T. Toxoid, P. toxoid plus inactivated poliovirus 1-3) and 3 weeks later on 11th September 2014, had positive responses to tetanus (specific IgG-0.64), and diphtheria (specific IgG - 0.6). Haemophilus B specific IgG was 4.77 but there was no response to pertussis (specific IgG - 1.18). Serum free light chain assay indicated elevated S-kappa at 33.40 (3.3-19.4), S-lamda normal at 6.36 (5.71-26) and elevated Kappa/Lamda ratio of 5.25 (0.26-1.65)
MGUS (monoclonal gammopathy of uncertain significance) is commonly associated with immune paresis, and the reduced serum IgM and IgG2 subclass levels may represent partial immune paresis in this regard. Furthermore, she had good responses to vaccination with both protein and polysaccharide antigens, suggesting functional humeral B-cell capacity for antibody production. I therefore felt that there was insufficient evidence of immune deficiency due to a late onset primary immune deficiency at this stage. Although she had received stabilized human serum from a hematologist in the past because of recurrent sinusitis one could also not make an argument for immunoglobulin replacement therapy given that, despite strong vaccination-induced IgG antibodies to S. Pneumonia documented in May, this organism was cultured from her sputum on the 16 September and 13 October 2014, and most likely came from her sinuses, which had clear evidence of sepsis on CT scan.
The problem is that repeat IgG ELIZA on 03 December 2014 indicated reduced values for H. Influenza and C. Tetanus which indicates that the response to vaccination as summarized below was not durable or sustained:
BASELINE April Post-Hiberix & Pneumovax 23 May Post-Boostrix September December
S. Pneumonia 13.32 >270 92.2
H. Influenza 1.92 3.07 4.77 0.95
C. Tetanus 0.02 0.02 0.64 0.09
C. Diphtheria 0.02 0.60
B. Pertussis 5.23 1.18
Does this then constitute evidence of bona fide antibody deficiency, and indicate that she may indeed benefit from Ig replacement therapy?
I'd appreciate any advice.
Many Thanks,
Stan
--
Stanley Ress
Emeritus Associate Professor of Medicine, UCT
UCT Private Academic hospital,
Anzio Road, Observatory,
Cape Town, 7925
South Africa
TEL:INTERN. + 2721-4421966 or 4421816
FAX: " + 2721-(0)865173095
Cell: 0833115482
email: stan.ress at uct.ac.za<mailto:stan.ress at uct.ac.za>
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