Cyclophosphamide-induced lupus flare?: the role of C4 and interferon-gamma in lupus flare
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Park, J.H. Kim, T.S. Ha, J.I. Shin" "autores" => array:4 [ 0 => array:3 [ "Iniciales" => "S.J." "apellidos" => "Park" "referencia" => array:1 [ 0 => array:2 [ "etiqueta" => "<span class="elsevierStyleSup">a</span>" "identificador" => "affa" ] ] ] 1 => array:3 [ "Iniciales" => "J.H." "apellidos" => "Kim" "referencia" => array:1 [ 0 => array:2 [ "etiqueta" => "<span class="elsevierStyleSup">b</span>" "identificador" => "affb" ] ] ] 2 => array:3 [ "Iniciales" => "T.S." "apellidos" => "Ha" "referencia" => array:1 [ 0 => array:2 [ "etiqueta" => "<span class="elsevierStyleSup">c</span>" "identificador" => "affc" ] ] ] 3 => array:4 [ "Iniciales" => "J.I." "apellidos" => "Shin" "email" => array:1 [ 0 => "shinji@yuhs.ac" ] "referencia" => array:1 [ 0 => array:2 [ "etiqueta" => "<span class="elsevierStyleSup">b</span>" "identificador" => "affb" ] ] ] ] "afiliaciones" => array:3 [ 0 => array:3 [ "entidad" => "Pediatrics Department, Ajou University School of Medicine, Suwon, Republic of Korea, " "etiqueta" => "<span class="elsevierStyleSup">a</span>" "identificador" => "affa" ] 1 => array:3 [ "entidad" => "Pediatrics Department, Yonsei University College of Medicine, Seoul, Republic of Korea, " "etiqueta" => "<span class="elsevierStyleSup">b</span>" "identificador" => "affb" ] 2 => array:3 [ "entidad" => "Pediatrics Department, Chungbuk National University College of Medicine, Cheongju, Republic of Korea, " "etiqueta" => "<span class="elsevierStyleSup">c</span>" "identificador" => "affc" ] ] ] ] "textoCompleto" => "<p class="elsevierStylePara"><span class="elsevierStyleBold">Dear Editor:</span></p><p class="elsevierStylePara">We read with great interest the contribution by Heras, et al.<span class="elsevierStyleSup">1</span>. They reported a significant case that seemed not to respond to intravenous (IV) cyclophosphamide (CPM) induction treatment at 1 g but to respond to increased CPM dose to 1.5 g. Reading the case report, we wondered whether CPM certainly induced the lupus flare or other mechanisms were involved in the pathogenesis. They speculated that the lupus flare might have been due to the initial underdosing of cyclophosphamide. This explanation is plausible, but we would like to say that lupus flares can occur during or after stopping CPM treatment, suggesting the possible pathomechanisms of lupus flare.</p><p class="elsevierStylePara">In the immunological test after the first treatment of IV CPM, the patient had increased C3 level, but C4 was decreased. According to a previous study by Ho, et al.<span class="elsevierStyleSup">2</span>, a decrease in C4 was associated with a concurrent increase in renal disease activity (p = 0.02). A decrease in C4 was especially associated with concurrent decreases in the hematocrit levels (p = 0.009), and previous increases in C3 were also associated with a higher frequency of decrease in platelet counts (p = 0.02). These data show that the renal and hematologic systemic lupus erythematosus (SLE) activity and flares are strongly associated with decreased C4.</p><p class="elsevierStylePara">Recently, Finke, et al.<span class="elsevierStyleSup">3</span> demonstrated that complement C4-deficient mice result in elevated intravascular levels of apoptotic DNA, targeted to the splenic marginal zone where it accumulates and induces type I interferon-gamma (IFN-γ). Type I IFN-γ 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>.</p><p class="elsevierStylePara">Therefore, we suggest that CPM is not an inducer but an inhibitor of lupus flare, and decreases in C4 and increased type I IFN-γ might play the central role in the development of lupus activity and flares. However, further studies are necessary to elucidate the exact molecular roles of complement deficiency and elevated levels of IFN-γ. The potential therapeutic antibodies directed to either type I IFN-γ or IFN α chain of the receptor 1 (IFNAR1)/IFNAR2 should also be further evaluated in the future.</p>" "pdfFichero" => "P1-E524-S3360-A10942-EN.pdf" "tienePdf" => true "bibliografia" => array:2 [ "titulo" => "Bibliography" "seccion" => array:1 [ 0 => array:1 [ "bibliografiaReferencia" => array:4 [ 0 => array:3 [ "identificador" => "bib1" "etiqueta" => "1" "referencia" => array:1 [ 0 => array:3 [ "referenciaCompleta" => "Heras M, Saiz A, Fernández-Reyes MJ, Sánchez R, Zurita P, Urrego C. Cyclophosphamide-induced lupus flare in diffuse proliferative lupus nephropathy. Nefrologia 2011;22;31." "contribucion" => array:1 [ 0 => null ] "host" => array:1 [ 0 => null ] ] ] ] 1 => array:3 [ "identificador" => "bib2" "etiqueta" => "2" "referencia" => array:1 [ 0 => array:3 [ "referenciaCompleta" => "Ho A, Barr SG, Magder LS, Petri M. A decrease in complement is associated with increased renal and hematologic activity in patients with systemic lupus erythematosus. Arthritis Rheum 2001;44:2350-7. <a href="http://www.ncbi.nlm.nih.gov/pubmed/11665976" target="_blank">[Pubmed]</a>" "contribucion" => array:1 [ 0 => null ] "host" => array:1 [ 0 => null ] ] ] ] 2 => array:3 [ "identificador" => "bib3" "etiqueta" => "3" "referencia" => array:1 [ 0 => array:3 [ "referenciaCompleta" => "Finke D, Randers K, Hoerster R, Hennig H, Zawatzky R, Marion T, et al. Elevated levels of endogenous apoptotic DNA and IFN-alpha in complement C4-deficient mice: implications for induction of systemic lupus erythematosus. Eur J Immunol 2007;37:1702-9. <a href="http://www.ncbi.nlm.nih.gov/pubmed/17506029" target="_blank">[Pubmed]</a>" "contribucion" => array:1 [ 0 => null ] "host" => array:1 [ 0 => null ] ] ] ] 3 => array:3 [ "identificador" => "bib4" "etiqueta" => "4" "referencia" => array:1 [ 0 => array:3 [ "referenciaCompleta" => "Dall'era MC, Cardarelli PM, Preston BT, Witte A, Davis JC Jr. Type I interferon correlates with serological and clinical manifestations of SLE. Ann Rheum Dis 2005;64:1692-7. <a href="http://www.ncbi.nlm.nih.gov/pubmed/15843451" target="_blank">[Pubmed]</a>" "contribucion" => array:1 [ 0 => null ] "host" => array:1 [ 0 => null ] ] ] ] ] ] ] ] ] "idiomaDefecto" => "en" "url" => "/20132514/0000003100000005/v0_201502091634/X2013251411052455/v0_201502091634/en/main.assets" "Apartado" => array:4 [ "identificador" => "35439" "tipo" => "SECCION" "en" => array:2 [ "titulo" => "Letters to the Editor - Comments on published articles" "idiomaDefecto" => true ] "idiomaDefecto" => "en" ] "PDF" => "https://static.elsevier.es/multimedia/20132514/0000003100000005/v0_201502091634/X2013251411052455/v0_201502091634/en/P1-E524-S3360-A10942-EN.pdf?idApp=UINPBA000064&text.app=https://revistanefrologia.com/" "EPUB" => "https://multimedia.elsevier.es/PublicationsMultimediaV1/item/epub/X2013251411052455?idApp=UINPBA000064" ]
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