[CIS PIDD] [cis-pidd] treatment for IL12Rb1 deficiency

[Edgar, David]

Dear Elena
We previously published experience of use of high dose IFN gamma in DN IFNgR deficiency in a child with Disseminated BCG. We gradually incremented dosage to 250mcg/m2 with no adverse effects. We did note however that when we achieved effective doses, the patient experienced fever and some headache on the evening of treatments. We monitored renal and hepatic function along with inflammatory markers. Duration and details available at:
Smyth AE et al. Eur J Paeds 2006 Jan; 165(1):71-2
Hope this helps
David
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From: Elena Hsieh [mailto:whsieh at stanford.edu]
Sent: Friday, May 16, 2014 03:48 AM
To: CIS-PIDD <cis-pidd at lists.clinimmsoc.org>
Subject: [cis-pidd] treatment for IL12Rb1 deficiency


Hi everybody,

We would like to ask your opinion for treatment approaches for BCGosis for a patient with IL12Rb1 chain deficiency.

This is a 3.5yr-old with a compound heterozygous IL-12 receptor beta1 chain deficiency complicated by BCGosis involving mainly pelvic and inguinal LN. His BCGosis has been treated with a combination of INH, rifampin, levofloxacin, clarithromycin for antimicrobial therapy. He also received interferon gamma 50 mcg/M2 3 times a week subcutaneously between February 2012 and April 2013. We saw him in July 2013 and performed antimicrobial serum drug levels sent to National Jewish, which were all somewhat low.  He also reinitiated IFN-gamma at that point at the above dose, and is currently still on it.  Recently, his MRI demonstrated slight increase in size of the R pelvic side LN, and his other para-aortic and mesenteric LNs are stable.  He’s clinically doing reasonably well, growing and developing appropriately. We plan to send blood to Wisconsin for flow cytometry analysis of any residual IL12R surface expression and function (STAT1, STAT4).

Here are our questions:

-        Has anyone been able to definitively treat BCGosis in the setting of Th1 immune defects using the combo of antimicrobials plus interferon-gamma?

-        If so, what dose and duration of IFN-gamma was used?

-        Are there alternative approaches we might consider other than HCT or gene therapy?

-        Paper from Dr. Cassonava’s group (Alangari et al., Clinical and Developmental Immunology, 2010) suggested that for IL12b1 deficiency patients, 200ug/M2 dose is effective and not at lower doses.  If anyone has used these higher doses, what are the toxicities we should monitor? (currently renal and liver function intact)

We appreciate your input.

Thanks.

Elena Hsieh, MD

Allergy and Immunology Fellow

Stanford University

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