Table 1.
Current biologicals inlcuding those most commonly used in autoimmune complications of PID
| Target | Agent | Structure | Approved indication by FDA | Used in PID patients off label or in clinical trials |
| Cellular lymphocytes | ||||
| CD52 | Alemtuzumab | anti-CD52 mAb | MS | pt with HLH |
| B cells | ||||
| CD20 | Rituximab | chimeric mouse/human anti-CD20 mAb | RA, polyJIA | ITP, AIHA, GLILD (pts with CVID/CID, APDS/PASLI) |
| Ofatumumab | human anti-CD20 mAb | adult refractory CLL | ||
| Obinutuzumab | humanized anti-CD20mAb | adult de novo CLL | ||
| CD22 | Epratuzumab | humanized anti-CD22mAb | B cell malignancies | |
| BAFF | Belimumab | human anti-BAFF mAb | SLE | |
| CD38 | Daratumumab | human anti-CD38 mAb | MM | AIHA (pts with WAS s/p HSCT) |
| Proteosome inhibitor | Bortezomib | pyrazine and boronic acid derivative | MM, MCL | |
| Carfilzomib | epoxomicinderivate | MM | ||
| Ixazomib | second generation boron containing peptide | MM, MCL | ||
| T cells | ||||
| m-TOR | Sirolimus (rapamycin) | S6K/m-TOR inhibitor | LAM, T/OR | ITP, AIHA (pts with CTLA4/LRBA def, ALPS, APDS) |
| m-TOR | Everolimus | S6K/m-TOR inhibitor | BrCA, TS, T/OR | CTLA4/LRBA def |
| IMD | Myocphenolic acid | reversible inhibitor of IMD | kidney, heart, liver transplant | ITP, AIHA (pts with CTLA4/LRBA def, ALPS, APDS) |
| CD28 | Abatacept | human CTLA4-IgG fusion protein with extracellular domain of CTLA4 and IgG1 Fc | RA, polyJIA | pts with CTLA4, LRBA def |
| p110δ | Leniolisib (CDZ173) | small-molecule inhibitor of p110δ | n.a. | pts with APDS/PASLI |
| Complement | ||||
| Complement C5 | Eculizumab | recombinant humanized IgG2 anti-C5 mAb | generalized MG, PNH | |
| Cytokines and receptors | ||||
| TNFα | Etanercept | soluable TNFα receptor IgG Fc fusion protein | RA | AInD (pts with TRAPS) |
| Infliximab | human mouse chimeric anti-TNFα mAb | RA, UC | CVID with GLILD | |
| Adalimumab | Fully human anti-TNFα mAb | RA, UC | ||
| Golimumab | Fully human anti-TNFα mAb | RA, UC | ||
| Certolizumab pegol | Humanized pegylated Fab’ fragment | RA, CD | ||
| IL-1β pathway | Anakinra | Recombinant IL-1R antagonist | RA, CAPS | CGD and AInD (pts with CAPS, FMF, TRAPS, HIDS, DIRA) |
| Rilonacept | fusion of IL-1R and IL-1R accessory protein | CAPS | AInD (CAPS such as FCAS, MWS, less effective in NOMID) | |
| Canakinumab | mAb to IL-1β | JIA, CAPS | ||
| IL-6R | Tocilizumab | Humanized IL-6R antagonist | RA, JIA | pt with STAT3 GOF |
| IL-12/IL-23 | Ustekinumab | Fully human anti-IL-12/IL-23 mAb (anti-p40) | PsA | CGD, LAD-1 |
| IL-17 | Secukinumab | Fully human anti-IL-17 mAb | PsO | |
| IFNγ | Emapalumab (NI-0501) | Fully human anti-IFNγ mAb | n.a. | AInD with HLH and NLRC4 mutation |
| JAK1/2 | Ruxolitinib | small molecule JAK (1-2) inhibitor | RA, PV | STAT1 and STAT3 GOF |
| JAK1/2 | Baricitinib | small molecule JAK (1-2) inhibitor | RA | STAT1 GOF and CANDLE syndrome |
| JAK1/3 | Tofacitinib | small molecule JAK (1-3) inhibitor | RA, PsA, UC | STAT3-GOF STAT1-GOF CANDLE syndrome |
| JAK3 | Decernotinib | small molecule JAK3 inhibitor | n.a. | RA |
| PD-1 | Nivolumab | human anti-PD-1 mAb | M | |
| PD-1 | Pembrolizumab | human anti-PD-1 mAb | UC, M, CA | |
| CXCR4 | Plerixafor | small molecule inhibitor (bicylam) | T for MM or NHL | WHIM syndrome |
| CXCR4 | Mavorixafor (X4P-001) | n.a. | n.a. | WHIM syndrome |
AInD, autoinflammatory disorder; BAFF, B cell acivating factor; BrCA, breast cancer; CA, cancer; CD, Crohns disease, CGD, chronic granulomatous disease; CTLA, cytotoxic T lymphocyte antigen; FDA, Food and Drug Administration; GLILD, granulomatous lymphocytic interstitial lung disease; IMD, inosine monophosphate dehydrogenase; JAK, janus kinase; JIA, juvenile idiopathic arthritis; IL-6R, interleukin 6 receptor; LAD-1, leukocyte adhesion defect 1; LAM, lymphangioleiomyomatosis; LRBA, lipopolysaccharide-responsive and beige-like anchor protein deficiency; m-TOR, mechanistic target of rapamycin; MCL, mantle cell lymphoma; MG, myasthenia gravis; MM, myeloma multiplex; M, melanoma; MS, mulitple sclerosis; PNH, paroxysmal nocturnal hemoglobinuria; PsA, psoriatic arthritis; Pso, psoriasis; S6K, Serine/threonine protein kinase; Pts, patients; PV, polycythemia vera; T/OR, transplant and organ rejection; TS, tuberous sclerosis; UC, ulcerative colitis.