‘”Why me, why now?” Using clinical immunology and epidemiology to explain who gets nontuberculous mycobacterial infection

Table 1 Potential effects of targeted small molecule/monoclonal agents on risk of NTM Infection

		Element of NTM immune response targeted?
Target	Example(s)	T cells	Mononuclear phagocytes	Key cytokines	Other Th1 cytokines	Theoretical risk for NTM †
TNF	Infliximab Certolizumab Adalimumab Etanercept Golimumab	N	N	Y	N	+++
IL-12/23	Ustekinumab	N	N	Y	N	+++
JAK	Ruxolitinib Tofacitinib	?	Y	Y	N	+++
CD52	Alemtuzumab	Y	Y	N	?	++
CD25/IL2R	Basiliximab Daclizumab	Y	?	N	?	++
CD3	Muromonab	Y	N	N	N	++
α4-integrin component	Natalizumab	Y	Y	N	N	++
IL-6R	Tocilizumab	N	N	N	Y	+
CTLA-4 (agonist)	Abatacept Belatacept	N	Y	?	Y	+
IL-1R1/IL-1β	Anakinra Rilonacept	N	N	N	Y	+
CD30	Brentuximab	Y	N	N	N	±
RANKL	Denosumab	Y	Y	N	N	±
CD20	Rituximab * Ofatumumab *	N	N	N	N	-
BLyS/BAFF	Belimumab *	N	?	N	N	-
Btk	Ibrutinib *	N	?	N	N	-
HER-2/erbB	Trastuzumab Pertuzumab Erlotinib	N	N	N	N	-
VEGF/VEGFR	Bevacizumab Ranibizumab Aflibercept Axitinib Lapatinib	N	N	N	N	-
EGFR	Panitumumab Afatinib Gefitinib	N	N	N	N	-
BcrAbl	Bosutinib Nilotinib	N	N	N	N	-
C5	Eculizumab	N	N	N	N	-
IgE	Omalizumab	N	N	N	N	-
GPIIb/IIIa	Abciximab	N	N	N	N	-

* Target B cells – note risk of hypogammaglobulinemia and secondary bronchiectasis
† +++ very significant risk, ++ significant risk, + some risk, ± unclear risk, − no risk
Y = Yes, N = No, ? = possible
TNF, tumour necrosis factor; IL, interleukin; JAK, Janus activated kinase; CD, cluster of differentiation; CTLA-4, cytotoxic T-lymphocyte-associated protein 4; RANKL, Receptor activator of nuclear factor kappa-B ligand; BLyS, B lymphocyte stimulator; BAFF, B cell activating factor; Btk, Bruton’s tyrosine kinase; HER-2, Human epidermal growth factor receptor 2; VEGF(R), vascular endothelial growth factor (receptor); EGFR, epidermal growth factor receptor; C5, complement component C5; IgE, Immunoglobulin E; GPIIb/IIIa, Glycoprotein IIb/IIIa; NTM, nontuberculous mycobacteria; Th1, T helper 1

ISSN: 1741-7015