Variable outcome of experimental interferon-gamma therapy of disseminated Bacillus Calmette-Guerin infection in two unrelated interleukin-12Rbeta1-deficient Slovakian children.
Mycobacterium bovis Bacillus Calmette-Guerin (BCG) is an attenuated live vaccine that may cause life-threatening clinical disease in children with impaired immunity. In particular, patients with any of the nine known inherited disorders of the interleukin-12/23 interferon-gamma (IL-12/23-IFNgamma) axis are highly vulnerable to BCG. We describe two unrelated young Slovakian children suffering from disseminated BCG infection which developed shortly after routine BCG vaccination after birth. During treatment with selected anti-BCG antibiotics, resistance against several of these drugs developed. In both children, interleukin-12/23 receptor beta1 (IL-12/23Rbeta1) deficiency was diagnosed. Thus, in addition to chemotherapy, immunomodulatory treatment with recombinant IFN-gamma was performed as the pathogenesis of BCG disease in IL-12Rbeta1 deficiency involves impaired IL-12- and IL-23-dependent IFN-gamma production by lymphocytes. One child responded to treatment and is presently doing well whereas the second patient died.


CONCLUSIONS
The marked variability of outcome of disseminated Bacillus Calmette-Guerin disease in interleukin-12/23 receptor beta1-deficient children sharing the same ethnic origin and exposed to a similar environment as presented in these case reports has to be taken into consideration for diagnosis and treatment of infections due to this genetic defect.
Ulrichs
Timo
T
Department of Immunology, Max-Planck-Institute for Infection Biology, Berlin, Germany.
Fieschi
Claire
C
Nevicka
Eva
E
Hahn
Helmut
H
Brezina
Martin
M
Kaufmann
Stefan H E
SH
Casanova
Jean-Laurent
JL
Frecerova
Klara
K
D000818:Animals; D000998:Antiviral Agents / Q000627:therapeutic use*; D002417:Cattle; D002675:Child, Preschool; D024901:Drug Resistance, Multiple, Bacterial; D005260:Female; D006801:Humans; D007167:Immunotherapy / Q000379:methods; D007371:Interferon-gamma / Q000627:therapeutic use*; D009163:Mycobacterium bovis / Q000302:isolation & purification; D018123:Receptors, Interleukin / Q000172:deficiency*; D018154:Slovakia / Q000208:ethnology; D014380:Tuberculosis, Bovine / Q000276:immunology / Q000628:therapy*
D000998:Antiviral Agents; D018123:Receptors, Interleukin; D007371:Interferon-gamma