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Cyclophosphamide-induced lupus flare?: the role of C4 and interferon-gamma in lupus flare
Cyclophosphamide-induced lupus flare?: the role of C4 and interferon-gamma in lupus flare
S.J.. Parka, J.H.. Kimb, T.S.. Hac, J.I.. Shinb
a Pediatrics Department, Ajou University School of Medicine, Suwon, Republic of Korea,
b Pediatrics Department, Yonsei University College of Medicine, Seoul, Republic of Korea,
c Pediatrics Department, Chungbuk National University College of Medicine, Cheongju, Republic of Korea,
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    "textoCompleto" => "<p class="elsevierStylePara"><span class="elsevierStyleBold">Dear Editor&#58;</span></p><p class="elsevierStylePara">We read with great interest the contribution by Heras&#44; et al&#46;<span class="elsevierStyleSup">1</span>&#46; They reported a significant case that seemed not to respond to intravenous &#40;IV&#41; cyclophosphamide &#40;CPM&#41; induction treatment at 1 g but to respond to increased CPM dose to 1&#46;5 g&#46; Reading the case report&#44; we wondered whether CPM certainly induced the lupus flare or other mechanisms were involved in the pathogenesis&#46; They speculated that the lupus flare might have been due to the initial underdosing of cyclophosphamide&#46; This explanation is plausible&#44; but we would like to say that lupus flares can occur during or after stopping CPM treatment&#44; suggesting the possible pathomechanisms of lupus flare&#46;</p><p class="elsevierStylePara">In the immunological test after the first treatment of IV CPM&#44; the patient had increased C3 level&#44; but C4 was decreased&#46; According to a previous study by Ho&#44; et al&#46;<span class="elsevierStyleSup">2</span>&#44; a decrease in C4 was associated with a concurrent increase in renal disease activity &#40;p &#61; 0&#46;02&#41;&#46; A decrease in C4 was especially associated with concurrent decreases in the hematocrit levels &#40;p &#61; 0&#46;009&#41;&#44; and previous increases in C3 were also associated with a higher frequency of decrease in platelet counts &#40;p &#61; 0&#46;02&#41;&#46; These data show that the renal and hematologic systemic lupus erythematosus &#40;SLE&#41; activity and flares are strongly associated with decreased C4&#46;</p><p class="elsevierStylePara">Recently&#44; Finke&#44; et al&#46;<span class="elsevierStyleSup">3</span> demonstrated that complement C4-deficient mice result in elevated intravascular levels of apoptotic DNA&#44; targeted to the splenic marginal zone where it accumulates and induces type I interferon-gamma &#40;IFN-&#947;&#41;&#46; Type I IFN-&#947; is important for the initiation and potentiation of SLE activity and correlated with the renal disease and the presence of cutaneous manifestations<span class="elsevierStyleSup">4</span>&#46;</p><p class="elsevierStylePara">Therefore&#44; we suggest that CPM is not an inducer but an inhibitor of lupus flare&#44; and decreases in C4 and increased type I IFN-&#947; might play the central role in the development of lupus activity and flares&#46; However&#44; further studies are necessary to elucidate the exact molecular roles of complement deficiency and elevated levels of IFN-&#947;&#46; The potential therapeutic antibodies directed to either type I IFN-&#947; or IFN &#945; chain of the receptor 1 &#40;IFNAR1&#41;&#47;IFNAR2 should also be further evaluated in the future&#46;</p>"
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