Page 729 - Clinical Immunology_ Principles and Practice ( PDFDrive )

702 Part SIX Systemic Immune Diseases

Two studies of monoclonal antibodies against IFN-α failed CONCLUSIONS
to demonstrate efficacy; a trial of an antibody to the IFN receptor
is under way. In the past several years much has been learned about genetic
Novel interventions directed at T cells include anti-CD40 susceptibility to SLE, and it is encouraging that many of the
antibodies, abatacept (CTLA4-Ig) in combination with cyclo- genes identified are associated with pathways that also have been
phosphamide for proliferative nephritis, and studies targeting implicated in disease pathogenesis. The role of B cells in disease
ICOS, an inducible T-cell costimulator. pathogenesis has been confirmed, but recent studies have also
Therapies in development for other autoimmune diseases highlighted the role of T cells, DCs, and neutrophils. Enhanced
may also prove useful in SLE. Eculizumab, currently approved understanding of each of these contributing factors and the
for paroxysmal nocturnal hemoglobinuria, is an antibody directed cross-talk between them has allowed identification of numerous
against C5 that blocks cleavage of C5 and the subsequent trig- potential therapeutic targets. The disappointing results from
gering of the complement cascade. Alicaforsen, an antisense clinical trials of immunobiological agents for lupus have
oligodeoxynucleotide that inhibits ICAM-1 expression, decreases highlighted the critical importance of study design and the
inflammation in both rheumatoid arthritis and Crohn disease. complexity of disease in humans. The overall goal in therapy
Efalizumab, a monoclonal antibody against CD11a (an LFA-1 must be to eliminate autoreactivity while maintaining immu-
subunit that interacts with ICAM-1), benefits patients with nocompetence. Among the challenges now faced are the careful
psoriasis. Although no chemokine-targeted therapies are in clinical phenotyping of patients to identify etiopathologically distinct
trial in lupus, a CCR1 antagonist slowed disease progression in subpopulations and new clinical trial designs to allow the use
a mouse model of lupus and has been tested in patients with of combinations of agents, each of which alone may have a
rheumatoid arthritis. FTY720, an agonist for the sphingosine 1 minor effect on disease course.
phosphate receptor that prevents egress of lymphocytes from
secondary lymphoid organs and inflamed tissues, has beneficial Please check your eBook at https://expertconsult.inkling.com/
effects in the MRL/lpr mouse model of lupus; it has been given for self-assessment questions. See inside cover for registration
to transplant recipients and to patients with multiple sclerosis. details.
The use of anti-TNF-α agents for SLE is inhibited by its lupus-like
effects in some patients. Paradoxically, TNF-α is involved in
renal inflammation in SLE, and short-term treatment with REFERENCES
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