Characteristics of patients with monoclonal Ig in the context of HCV infection
| Patient clinical contextM . | Characteristics of HCV infection . | Characteristics of the monoclonal Ig . | Evolution (follow-up 4.5 years) . | |||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Pt no. . | Sex . | Main pathology . | Age at diagnosisof mainpathology, y . | Age at diagnosisof HCVinfection, y . | Genotype . | HCV proteins recognized by serum Ig . | Age at diagnosisof monoclonalIg, y . | Isotype . | Quantity, g/L . | Specificity . | ||||
| NS-3 . | NS-4 . | C22-3 core . | NS-5 . | |||||||||||
| 2 | M | Type II cryoglobulinemia | 70 | 58*† | 2a | +/− | + | +++ | +/− | 72 | G λ | 26 | nd | Liver cirrhosis with elevated AFP (age 59) |
| 8 | M | HIV infection | 23 | 28† | 2f | + | + | +++ | +/− | 40 | G κ | 24 | Core | Treated‡ (age 46) |
| Inflammatory bowel disease | 38 | |||||||||||||
| 9 | M | B hemophilia | childhood | Treated,‡ liver cirrhosis (age 51) | ||||||||||
| HIV infection | 28 | 40† | 3a | +/− | ++ | +++ | +/− | 45 | G κ | 10.6 | NS-4 | |||
| 10 | F | Lichen planus | 59 | 36*† | 1b | − | +/− | + | − | 64 | G κ | 9.5 | nd | Anti-HCV treatment‡ (age 70) |
| 12 | M | Type II cryoglobulinemia | 62 | 75† | 2f | − | +/− | +++ | − | 75 | G κ | 17.4 | Core | Dead from heart disease (age 75) |
| Myocardial infarction | 65 | |||||||||||||
| 14 | F | MGUS | 47 | 46† | 5a | +++ | +++ | +++ | +++ | 47 | G λ | 16.3 | nd | Not treated, monoclonal Ig stable (age 55) |
| 19 | F | Kidney failure (transplantation) | 28 | 27† | 1b | +/− | +++ | − | − | 36 | G κ | 17.8 | NS-4 | Alive (age 43), no information |
| 29 | ||||||||||||||
| 20 | F | Type II cryoglobulinemia | 75 | 71† | 2k | +/− | +/− | ++ | ++ | 76 | M κ | 22 | Core | Dead (age 82) |
| 21 | F | Multiple myeloma | 76 | 76† | 2k | − | +/− | +++ | − | 76 | A κ | 16.1 | Core | Dead from MM (age 79) |
| 29 | F | Heart/kidney failure (transplantation) | 58 | |||||||||||
| 65 | 74† | 1b | +/− | +/− | +++ | − | 75 | A λ | 12.6 | Not HCV | Alive (age 80) | |||
| 1§ | M | Plasma-cell leukemia | 32 | 32† | 1a | +++ | +++ | +++ | ++ | 32 | G κ | 15.5 | Core | Dead from PCL (age 32) |
| Patient clinical contextM . | Characteristics of HCV infection . | Characteristics of the monoclonal Ig . | Evolution (follow-up 4.5 years) . | |||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Pt no. . | Sex . | Main pathology . | Age at diagnosisof mainpathology, y . | Age at diagnosisof HCVinfection, y . | Genotype . | HCV proteins recognized by serum Ig . | Age at diagnosisof monoclonalIg, y . | Isotype . | Quantity, g/L . | Specificity . | ||||
| NS-3 . | NS-4 . | C22-3 core . | NS-5 . | |||||||||||
| 2 | M | Type II cryoglobulinemia | 70 | 58*† | 2a | +/− | + | +++ | +/− | 72 | G λ | 26 | nd | Liver cirrhosis with elevated AFP (age 59) |
| 8 | M | HIV infection | 23 | 28† | 2f | + | + | +++ | +/− | 40 | G κ | 24 | Core | Treated‡ (age 46) |
| Inflammatory bowel disease | 38 | |||||||||||||
| 9 | M | B hemophilia | childhood | Treated,‡ liver cirrhosis (age 51) | ||||||||||
| HIV infection | 28 | 40† | 3a | +/− | ++ | +++ | +/− | 45 | G κ | 10.6 | NS-4 | |||
| 10 | F | Lichen planus | 59 | 36*† | 1b | − | +/− | + | − | 64 | G κ | 9.5 | nd | Anti-HCV treatment‡ (age 70) |
| 12 | M | Type II cryoglobulinemia | 62 | 75† | 2f | − | +/− | +++ | − | 75 | G κ | 17.4 | Core | Dead from heart disease (age 75) |
| Myocardial infarction | 65 | |||||||||||||
| 14 | F | MGUS | 47 | 46† | 5a | +++ | +++ | +++ | +++ | 47 | G λ | 16.3 | nd | Not treated, monoclonal Ig stable (age 55) |
| 19 | F | Kidney failure (transplantation) | 28 | 27† | 1b | +/− | +++ | − | − | 36 | G κ | 17.8 | NS-4 | Alive (age 43), no information |
| 29 | ||||||||||||||
| 20 | F | Type II cryoglobulinemia | 75 | 71† | 2k | +/− | +/− | ++ | ++ | 76 | M κ | 22 | Core | Dead (age 82) |
| 21 | F | Multiple myeloma | 76 | 76† | 2k | − | +/− | +++ | − | 76 | A κ | 16.1 | Core | Dead from MM (age 79) |
| 29 | F | Heart/kidney failure (transplantation) | 58 | |||||||||||
| 65 | 74† | 1b | +/− | +/− | +++ | − | 75 | A λ | 12.6 | Not HCV | Alive (age 80) | |||
| 1§ | M | Plasma-cell leukemia | 32 | 32† | 1a | +++ | +++ | +++ | ++ | 32 | G κ | 15.5 | Core | Dead from PCL (age 32) |
Pt indicates patient; M, male; F, female; MM, multiple myeloma; nd, not determined (purification not achieved); MGUS, monoclonal gammopathy of unknown significance; and AFP, alpha fetoprotein.
Diagnosis of HCV infection was established using qRT-PCR (Cobas Amplicor HCV; Roche, Basel, Switzerland) to detect presence of HCV mRNA in serum, and recombinant immunoblot assay (RIBA III; Ortho Diagnostic Systems, Levallois-Perret, France) to detects Igs directed against HCV nonstructural proteins NS-3, NS-4, NS-5, and fragment C22-3 of the core protein. Viral genotype was established by sequencing of HCV gene NS-5b.
Patients 2 and 10 had a history of viral hepatitis at age 58 and 36, respectively. Monoclonal Ig detection and typing included serum electrophoresis performed on agarose gels (Hydrasys; Sebia, Evry, France) or capillary electrophoresis (Capillarys; Sebia). Serum monoclonal Ig were typed by immunofixation (Hydrasis; Sebia). Monoclonal Ig purification was performed by first separating monoclonal Ig from polyclonal Igs and beta globulins by electric charge, using electrophoresis on agarose gels (kit Paragon SPE-II; Beckman Coulter, Villepinte, France). Gel bands corresponding to monoclonal or polyclonal Igs were carefully cut and proteins were eluted from gels into PBS. Purity of each protein fraction was analyzed by immunofixation (SAS-MX; Helena Biosciences, Gateshead, United Kingdom) or/and by isoelectrofocusing and immunoblotting. For 3 patients, presence of polyclonal Igs prevented complete purification of the monoclonal Ig. Serum and eluted protein fractions were subjected to RIBA III immunoblot assay to determine their specificity (anti-NS-3, NS-4, NS-5, or C22-3 core protein).
The monoclonal Ig became undetectable under antiviral treatment (patients 8, 9, and 10).
For reference 4.