614e2a6e3d0a726886f59d17bf498220 pmc_11508573.pdf 35ac08f00817df24c315fb7987fa85186959eef4 pmc_11508573.pdf 9e9457d79f77463d90a0a0ca821f85ed436ef53b20fe368c5246142d05dbbd97 pmc_11508573.pdf Title: Clinical and Serological Profiles in Cryoglobulinemia: Analysis of Isotypes and Etiologies Subject: Objectives: Cryoglobulinemia (CG) is marked by abnormal immunoglobulins (Ig) in serum, precipitating at temperatures below 37 C. Current classification categorizes CG into three subtypes (types I, II, and III) based on Ig clonality. The features distinguishing patients with CG based on their etiology remain unidentified. Aiming to characterize clinical and serological profiles of CG individuals, we conducted an observational analysis of a large cohort of patients and compared their characteristics based on underlying causes: hepatovirus (HV) infections, rheumatic diseases (RD), hematological disorders, and unidentified etiology (essential CG). Methods: We analyzed 252 cryoglobulin-positive serum samples from 182 patients and classified these into the four etiological groups. A separate sub-analysis was carried out for 10 patients meeting criteria for multiple diseases. We collected demographic, clinical, and laboratory data: CG characterization, complement (C3 and C4) levels, antinuclear antibodies (ANA), and rheumatoid factor (RF). Kruskal–Wallis and Wilcoxon–Mann–Whitney U-tests were used for comparisons. Results: Most patients (93.3%) had mixed cryoglobulinemia (types II + III), with 6.7% having type I. HV infection, predominantly hepatitis C, was the main (52.9%) associated condition within the cohort, followed by rheumatic (27.3%) and hematological (9.8%) disorders. In our cohort, ANA were frequent (45.3%) and often associated with RF positivity (43.6%) and decreased complement levels (C3: 42.4%, C4: 32.5%). Essential CG and CG associated with RD had a higher prevalence of cutaneous manifestations (p < 0.01) and renal involvement (p = 0.017). Hematological disorder-related CG showed higher cryoglobulin and RF concentrations (p < 0.01), despite milder symptoms. Conclusions: Our study underscores a mixed prevalence of CG across disease subgroups, with hepatitis-C virus as the primary factor, followed by rheumatic and hematological disorders. Four clinical and serological profiles of CG were identified based on their etiologies. Keywords: cryoglobulinemia; vasculitis; hepatitis C; rheumatic disease; hematological disease Author: Helena Codes-Méndez, Sicylle Jeria, Hye-Sang Park, Patricia Moya, Berta Magallares-López, Elisabeth Moltó, Yolanda Álvaro, Anais Mariscal, Esther Moga, Jose Luis Tandaipan, César Díaz-Torne, Ana Laiz, Luis Sainz, Ivan Castellví and Hector Corominas Creator: LaTeX with hyperref Producer: pdfTeX-1.40.25 CreationDate: Fri Oct 11 15:45:16 2024 CEST ModDate: Fri Oct 11 15:48:55 2024 CEST Custom Metadata: no Metadata Stream: no Tagged: no UserProperties: no Suspects: no Form: none JavaScript: no Pages: 12 Encrypted: no Page size: 595.276 x 841.89 pts (A4) Page rot: 0 File size: 286538 bytes Optimized: no PDF version: 1.7 name type encoding emb sub uni object ID ------------------------------------ ----------------- ---------------- --- --- --- --------- QZKPTP+VnURWPalladioL-Bold Type 1 Custom yes yes yes 10 0 ZUTBBH+URWPalladioL-Bold Type 1 Custom yes yes yes 16 0 VZQDXI+URWPalladioL-Roma Type 1 Custom yes yes yes 22 0 UDZNBR+URWPalladioL-Ital Type 1 Custom yes yes yes 27 0 UDZZSY+CMSY10 Type 1 Builtin yes yes yes 32 0 IYDCBB+VnURWPalladioL Type 1 Custom yes yes yes 37 0 XPUSBJ+TimesNewRomanPS-BoldItalicMT Type 1C WinAnsi yes yes no 53 0 BSDWLC+TimesNewRomanPSMT Type 1C WinAnsi yes yes no 56 0 URYLRZ+URWPalladioL-BoldItal Type 1 Custom yes yes yes 82 0 QHMYDZ+wasy8 Type 1 Builtin yes yes yes 87 0 Jhove (Rel. 1.28.0, 2023-05-18) Date: 2025-02-06 02:46:56 CET RepresentationInformation: pmc_11508573.pdf ReportingModule: PDF-hul, Rel. 1.12.4 (2023-03-16) LastModified: 2025-01-11 02:30:29 CET Size: 286538 Format: PDF Version: 1.7 Status: Well-Formed and valid SignatureMatches: PDF-hul MIMEtype: application/pdf PDFMetadata: Objects: 294 FreeObjects: 1 IncrementalUpdates: 0 DocumentCatalog: PageLayout: SinglePage PageMode: UseNone Outlines: Item: Title: Introduction Destination: section.1 Item: Title: Materials and Methods Destination: section.2 Children: Item: Title: Study Population Destination: subsection.2.1 Item: Title: Data Collection and Variables Destination: subsection.2.2 Item: Title: Laboratory Investigation of Cryoglobulinemia and Serum Biomarkers Destination: subsection.2.3 Item: Title: Statistical Analysis Destination: subsection.2.4 Item: Title: Results Destination: section.3 Children: Item: Title: Baseline Clinical Characteristics and the Distribution of Biomarkers according to Disease Subgroups Destination: subsection.3.1 Item: Title: Hepatotropic Viruses’ Infection Destination: subsection.3.2 Item: Title: Rheumatic Diseases Destination: subsection.3.3 Item: Title: Hematological Diseases Destination: subsection.3.4 Item: Title: Essential Cryoglobulinemia Destination: subsection.3.5 Item: Title: Analysis of 10 Patients Meeting Diagnostic Criteria across Multiple Disease Subgroups Destination: subsection.3.6 Item: Title: Discussion Destination: section.4 Item: Title: References Destination: section.5 Info: Title: Clinical and Serological Profiles in Cryoglobulinemia: Analysis of Isotypes and Etiologies Author: Helena Codes-Méndez, Sicylle Jeria, Hye-Sang Park, Patricia Moya, Berta Magallares-López, Elisabeth Moltó, Yolanda Álvaro, Anais Mariscal, Esther Moga, Jose Luis Tandaipan, César Díaz-Torne, Ana Laiz, Luis Sainz, Ivan Castellví and Hector Corominas Subject: Objectives: Cryoglobulinemia (CG) is marked by abnormal immunoglobulins (Ig) in serum, precipitating at temperatures below 37 C. Current classification categorizes CG into three subtypes (types I, II, and III) based on Ig clonality. The features distinguishing patients with CG based on their etiology remain unidentified. Aiming to characterize clinical and serological profiles of CG individuals, we conducted an observational analysis of a large cohort of patients and compared their characteristics based on underlying causes: hepatovirus (HV) infections, rheumatic diseases (RD), hematological disorders, and unidentified etiology (essential CG). Methods: We analyzed 252 cryoglobulin-positive serum samples from 182 patients and classified these into the four etiological groups. A separate sub-analysis was carried out for 10 patients meeting criteria for multiple diseases. We collected demographic, clinical, and laboratory data: CG characterization, complement (C3 and C4) levels, antinuclear antibodies (ANA), and rheumatoid factor (RF). Kruskal Wallis and Wilcoxon Mann Whitney U-tests were used for comparisons. Results: Most patients (93.3%) had mixed cryoglobulinemia (types II + III), with 6.7% having type I. HV infection, predominantly hepatitis C, was the main (52.9%) associated condition within the cohort, followed by rheumatic (27.3%) and hematological (9.8%) disorders. In our cohort, ANA were frequent (45.3%) and often associated with RF positivity (43.6%) and decreased complement levels (C3: 42.4%, C4: 32.5%). Essential CG and CG associated with RD had a higher prevalence of cutaneous manifestations (p < 0.01) and renal involvement (p = 0.017). Hematological disorder-related CG showed higher cryoglobulin and RF concentrations (p < 0.01), despite milder symptoms. Conclusions: Our study underscores a mixed prevalence of CG across disease subgroups, with hepatitis-C virus as the primary factor, followed by rheumatic and hematological disorders. Four clinical and serological profiles of CG were identified based on their etiologies. 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