{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,16]],"date-time":"2026-04-16T18:31:05Z","timestamp":1776364265098,"version":"3.51.2"},"reference-count":87,"publisher":"Public Library of Science (PLoS)","issue":"4","license":[{"start":{"date-parts":[[2026,4,16]],"date-time":"2026-04-16T00:00:00Z","timestamp":1776297600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"IDEXX Laboratories Inc., Westbrook, ME, USA"}],"content-domain":{"domain":["www.plosone.org"],"crossmark-restriction":false},"short-container-title":["PLoS One"],"abstract":"<jats:p>\n                    Circulating immune complexes (CIC) cause different organ lesions in canine leishmaniosis. This study aimed to measure CIC in dogs infected with\n                    <jats:italic>Leishmania (L.) infantum<\/jats:italic>\n                    in a non-endemic country and to analyze associations with disease parameters. Measurement of\n                    <jats:italic>Leishmania<\/jats:italic>\n                    -specific CIC was performed by a polyethylene glycol ELISA (cut-off: 0.274 optical density (OD)) every three months during a one-year study period in 52\n                    <jats:italic>L. infantum<\/jats:italic>\n                    -infected dogs. Each appointment included a physical examination, complete blood count, serum biochemistry including C-reactive protein, urinalysis,\n                    <jats:italic>L. infantum<\/jats:italic>\n                    PCR and antibody ELISA. Statistical analyses included Mann-Whitney U tests, a multivariable robust linear regression, Spearman correlation, univariable logistic regression, and a receiver operating characteristic (ROC) curve. CIC levels differed significantly between dogs with and without lymphadenopathy (\n                    <jats:italic>p<\/jats:italic>\n                    \u2009&lt;\u20090.01;\n                    <jats:italic>\u03b2<\/jats:italic>\n                    =\u22120.38; 95% CI: \u22120.52, \u22120.24), uveitis (\n                    <jats:italic>p<\/jats:italic>\n                    \u2009&lt;\u20090.01;\n                    <jats:italic>\u03b2=\u2212<\/jats:italic>\n                    0.52; 95% CI: \u22120.89, \u22120.15), seborrhea\/hypotrichosis (\n                    <jats:italic>p<\/jats:italic>\n                    \u2009=\u20090.04;\n                    <jats:italic>\u03b2<\/jats:italic>\n                    =\u22120.11; 95% CI: \u22120.21, \u22120.01), and skin nodules (\n                    <jats:italic>p<\/jats:italic>\n                    \u2009&lt;\u20090.01;\n                    <jats:italic>\u03b2<\/jats:italic>\n                    \u2009=\u20090.22; 95% CI: 0.13, 0.31). Significant moderate to strong correlations with CIC levels were found for\n                    <jats:italic>L. infantum<\/jats:italic>\n                    antibodies (\n                    <jats:italic>p<\/jats:italic>\n                    \u2009&lt;\u20090.01;\n                    <jats:italic>r<\/jats:italic>\n                    <jats:sub>s<\/jats:sub>\n                    \u2009=\u20090.65; 95% CI: 0.57, 0.72), globulin (\n                    <jats:italic>p<\/jats:italic>\n                    \u2009&lt;\u20090.01;\n                    <jats:italic>r<\/jats:italic>\n                    <jats:sub>s<\/jats:sub>\n                    \u2009=\u20090.60; 95% CI: 0.51, 0.68), albumin-to-globulin ratio\n                    <jats:italic>(p<\/jats:italic>\n                    \u2009&lt;\u20090.01;\n                    <jats:italic>r<\/jats:italic>\n                    <jats:sub>s<\/jats:sub>\n                    =\u22120.56; 95% CI: \u22120.65, \u22120.47) and total protein (\n                    <jats:italic>p<\/jats:italic>\n                    \u2009&lt;\u20090.01;\n                    <jats:italic>r<\/jats:italic>\n                    <jats:sub>s<\/jats:sub>\n                    \u2009=\u20090.46; 95% CI: 0.35, 0.56). CIC levels were significantly higher in dogs with positive lymph node PCR (\n                    <jats:italic>p<\/jats:italic>\n                    \u2009=\u20090.04) as well as in dogs with disease relapses (\n                    <jats:italic>p<\/jats:italic>\n                    \u2009&lt;\u20090.01). The ROC curve analysis revealed one highly specific cut-off value at 1.668 OD for differentiating between dogs with and without disease relapse (98% specificity; 60% sensitivity). Measurement of\n                    <jats:italic>Leishmania<\/jats:italic>\n                    -specific CIC is useful for monitoring dogs with\n                    <jats:italic>L. infantum<\/jats:italic>\n                    infections and for indicating disease relapse.\n                  <\/jats:p>","DOI":"10.1371\/journal.pone.0345948","type":"journal-article","created":{"date-parts":[[2026,4,16]],"date-time":"2026-04-16T17:28:02Z","timestamp":1776360482000},"page":"e0345948","update-policy":"https:\/\/doi.org\/10.1371\/journal.pone.corrections_policy","source":"Crossref","is-referenced-by-count":0,"title":["Circulating immune complexes in dogs with Leishmania infantum infection in a non-endemic country"],"prefix":"10.1371","volume":"21","author":[{"ORCID":"https:\/\/orcid.org\/0009-0001-2414-0054","authenticated-orcid":true,"given":"Melanie","family":"Kaempfle","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Katrin","family":"Hartmann","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6928-4089","authenticated-orcid":true,"given":"Yury","family":"Zablotski","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Roswitha","family":"Dorsch","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Nuria","family":"Parody","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4050-2577","authenticated-orcid":true,"given":"Jer\u00f3nimo","family":"Carn\u00e9s","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Mich\u00e8le","family":"Bergmann","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"340","published-online":{"date-parts":[[2026,4,16]]},"reference":[{"issue":"16","key":"pone.0345948.ref001","doi-asserted-by":"crossref","first-page":"399","DOI":"10.1136\/vr.100637","article-title":"Prognostic analytes in dogs with Leishmania infantum infection living in a non-endemic area","volume":"171","author":"K Geisweid","year":"2012","journal-title":"Vet Rec"},{"key":"pone.0345948.ref002","first-page":"1","article-title":"Revisiting immune complexes: key to understanding immune-related diseases","volume":"96","author":"N Aibara","year":"2020","journal-title":"Adv Clin Chem"},{"issue":"12","key":"pone.0345948.ref003","doi-asserted-by":"crossref","first-page":"1509","DOI":"10.1017\/S0031182021001189","article-title":"Serum antibodies blocked by glycan antigens in canine visceral leishmaniasis serology are mostly IgA immune complexes","volume":"148","author":"C Aparecida de Carvalho","year":"2021","journal-title":"Parasitology"},{"key":"pone.0345948.ref004","doi-asserted-by":"crossref","first-page":"48","DOI":"10.1186\/1756-3305-4-48","article-title":"The immunopathology of canine vector-borne diseases","volume":"4","author":"MJ Day","year":"2011","journal-title":"Parasit Vectors"},{"issue":"7","key":"pone.0345948.ref005","doi-asserted-by":"crossref","first-page":"329","DOI":"10.1111\/j.1365-3024.2006.00840.x","article-title":"Immunology of canine leishmaniasis","volume":"28","author":"CL Barbi\u00e9ri","year":"2006","journal-title":"Parasite Immunol"},{"key":"pone.0345948.ref006","doi-asserted-by":"crossref","first-page":"87","DOI":"10.1016\/j.vetpar.2019.05.006","article-title":"Canine visceral leishmaniasis biomarkers and their employment in vaccines","volume":"271","author":"RC Giunchetti","year":"2019","journal-title":"Vet Parasitol"},{"issue":"4","key":"pone.0345948.ref007","doi-asserted-by":"crossref","first-page":"335","DOI":"10.1080\/00034983.1988.11812255","article-title":"Glomerulonephritis in dogs with canine leishmaniasis","volume":"82","author":"T Benderitter","year":"1988","journal-title":"Ann Trop Med Parasitol"},{"issue":"4","key":"pone.0345948.ref008","doi-asserted-by":"crossref","first-page":"444","DOI":"10.1159\/000186348","article-title":"Renal involvement in canine leishmaniasis. 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