Cryogloculins were examined in a standardized manner in an unselected group of 35 patients with rheumatoid arthritis (RA) and 8 patients with RA complicated by cutaneous vasuclitis and neuropathy. Optimum conditions for detection and characterization of cryoglobulins were established; the proportion of resolubilized to total precipitable protein remained constant in an individual patient under these conditions. All 8 vascultis patients and 9 of 35 other patients with RA exhibited cryoglobulins; total protein and immunoglobin content were significantly higher in the cryoglobulins of patients with vasculitis. Immunoglobulins G and M constituted two-thirds and three-quarters of the total protein in the cryoglobulins from uncomplicated rheumatoid and vasculitis patients, respectively. Serum antiglobulin titers were higher, and serum C3 levels were lower, in vasculitis patients compared to rheumatoid patients without vasclitis. Anti-gamma globulin activity was detected in all cryoglobulins from vasculitis patients. Cryoglobulin IgG and IgM were polyclonal. Density gradient analyses demonstrated the majority of the cryoglobulin activity to reside in the 19S IgM fraction. There was no evidence of a light weight (8S) IgM. A monoclonal rheumatoid factor did not detect 7S-ANTI-7S complexes in the cryoprecipitates, but acid eluates from some cryoglobulins absorbed with insoluble IgG revealed an antiglobulin of the IgG class. Serial studies performed on vasculitis patients treated with cyclophosphamide disclosed a relationship between clinical evidence of vasculitis and the presence of cryoglobulins. The antigen (IgG) and antibody (largely IgM rheumatoid factor) nature of these cryglobulins is presented as evidence that the widespread vascular complications of RA are mediated, at least in part, by circulating immune complexes.
M Weisman, N Zvaifler
Title and authors | Publication | Year |
---|---|---|
Case report: a man with untreated rheumatoid arthritis, cryoglobulinemic vasculitis, membranous nephropathy and pulmonary sarcoidosis
Q Wang, JP Ruiz, PD Hart |
BMC Nephrology | 2020 |
Laboratory guidelines for the diagnosis of patients with cryoglobulinemic syndrome
A Mariscal-Rodríguez, LM Guimerans, M López-Trascasa, MH González, EM Naranjo |
Revista Clínica Española (English Edition) | 2019 |
Guía de laboratorio para el diagnóstico de pacientes con síndrome crioglobulinémico
A Mariscal-Rodríguez, LM Guimerans, M López-Trascasa, MH González, EM Naranjo |
Revista Clínica Española | 2018 |
Vasculitis associated with rheumatoid arthritis: a case-control study
A Makol, CS Crowson, DA Wetter, O Sokumbi, EL Matteson, KJ Warrington |
Rheumatology | 2014 |
Diagnostics and Treatment of Cryoglobulinaemia: It Takes Two to Tango
J Damoiseaux, JW Tervaert |
Clinical Reviews in Allergy & Immunology | 2013 |
Serum cryoglobulins and disease activity in systematic lupus erythematosus
M Karimifar, S Pourajam, A Tahmasebi, P Mottaghi |
Journal of research in medical sciences : the official journal of Isfahan University of Medical Sciences | 2013 |
Rheumatoid Factor, Complement, and Mixed Cryoglobulinemia
PD Gorevic |
Clinical and Developmental Immunology | 2012 |
Advances in Clinical Chemistry
M Mahler |
Advances in Clinical Chemistry Volume 54 | 2011 |
Advances in Immunology
E Pinaud, M Marquet, R Fiancette, S Péron, C Vincent-Fabert, Y Denizot, M Cogné |
Advances in Immunology Volume 110 | 2011 |
Skin ulcers in a patient with Sjögren's syndrome
SL Chapnick, PA Merkel |
Arthritis Care & Research | 2010 |
Establishment of reference values for immunoglobulins in the cryoprecipitate
P Vermeersch, K Gijbels, D Knockaert, D Blockmans, R Westhovens, G Mariën, X Bossuyt |
Clinical Immunology | 2008 |
Inhibition of cryogelation by the novel synthetic peptide (Gly–Arg–Lys–Lys–Thr): recognition site of extra domain A containing fibronectin for heparin in cryogelation
K Miyamoto, D Kobayashi, R Maeda, T Ito, T Komai |
International Journal of Biological Macromolecules | 2003 |
Vasculitis asociadas a enfermedades del tejido conectivo
GS Puigdemont, AV Palacín, XB Viscasillas |
Piel | 2003 |
Cryoglobulinemia vasculitis
P Cacoub, N Costedoat-Chalumeau, O Lidove, L Alric |
Current Opinion in Rheumatology | 2002 |
Novel plasma-separation dilayer gellan–gellan-sulfate adsorber for direct removal of extra domain A containing fibronectin from the blood of rheumatoid arthritis patients
K Miyamoto, K Sugihara, Y Abe, T Nobori, M Tokita, T Komai |
International Journal of Biological Macromolecules | 2002 |
Specific interactions between cryogel components: role of extra domain A containing fibronectin in cryogelation
K Miyamoto, N Kodera, H Umekawa, Y Furuichi, M Tokita, T Komai |
International Journal of Biological Macromolecules | 2002 |
Hydrodynamics of cryogelation
K Miyamoto, Y Shimonishi, M Tokita, T Komai |
International Journal of Biological Macromolecules | 2001 |
Cryoglobulinemia
O Trejo, M Ramos-Casals, M García-Carrasco, J Yagüe, S Jiménez, GD la Red, R Cervera, J Font, M Ingelmo |
Medicine | 2001 |
Development of a novel polycationic adsorbent for cryogel removal
K Miyamoto, R Uchiyama, M Tokita, M Yonekawa, A Kawamura, K Miyashita, E Sakashita, T Komai |
International Journal of Biological Macromolecules | 2001 |
Cryoglobulinemia in systemic lupus erythematosus: Prevalence and clinical characteristics in a series of 122 patients
M García-Carrasco, M Ramos-Casals, R Cervera, O Trejo, J Yagüe, A Sisó, S Jiménez, G la Red, J Font, M Ingelmo |
Seminars in Arthritis and Rheumatism | 2001 |
Mixed cryoglobulinemia: new concepts
M Ramos-Casals, O Trejo, M García-Carrasco, R Cervera, J Font |
Lupus | 2000 |
Temperature curves of different types of cryoglobulins
NA Konstantinova, IY Kulikova |
Bulletin of Experimental Biology and Medicine | 1999 |
Vasculitic Peripheral Ulcerative Keratitis
EM Messmer, CS Foster |
Survey of Ophthalmology | 1999 |
Evaluation of Cryoglobulins
U Kallemuchikkal, PD Gorevic |
Archives of pathology & laboratory medicine | 1999 |
CRYOGLOBULINEMIA: RECENT FINDINGS IN CUTANEOUS AND EXTRACUTANEOUS MANIFESTATIONS
MD Davis, WD Su |
International Journal of Dermatology | 1996 |
The Vasculitides
BM Ansell, PA Bacon, JT Lie, H Yazici |
1996 | |
Long-term results regarding the use of recombinant interferon alpha-2b in the treatment of II type mixed essential cryoglobulinemia
VM Lauta, MA Sangro |
Medical Oncology | 1995 |
Peripheral neuropathy with necrotizing vasculitis in rheumatoid arthritis
X Puéchal, G Said, P Hilliquin, J Coste, C Job-Deslandre, C Lacroix, CJ Menkès |
Arthritis & Rheumatism | 1995 |
Familial occurrence of two patients with malignant rheumatoid arthritis
K Yokoi, E Hosoi, M Nakanishi, K Umemoto, T Shigekiyo, S Saito |
Journal of Internal Medicine | 1994 |
The Sclera
CS Foster, MS de la Maza |
1994 | |
NEUROLOGIC COMPLICATIONS OF RHEUMATOID ARTHRITIS
DJ Chang, SA Paget |
Rheumatic diseases clinics of North America | 1993 |
Pathogenic significance of serum components in the development of autoimmune polyarthritis in MRL/Mp mice bearing the lymphoproliferation gene
J Itoh, M Nose, M Kyogoku |
The American Journal of Pathology | 1991 |
Clinical effects of interferon in patients with idiopathic mixed cryoglobulinemia
M Casato, B Laganà, A Giorgi, G Antonelli, F Dianzani |
European Journal of Haematology | 1990 |
Azathioprine, cyclophosphamide and chlorambucil
RA Luqmani, RG Palmer, PA Bacon |
Baillière's Clinical Rheumatology | 1990 |
Vasculitis Associated with Rheumatoid Arthritis
RS Vollertsen, DL Conn |
Rheumatic diseases clinics of North America | 1990 |
Factors predicting a poor life prognosis in rheumatoid arthritis: an eight year prospective study
CC Erhardt, PA Mumford, PJ Venables, RN Maini |
Annals of the rheumatic diseases | 1989 |
Reappraisal of the clinical expression of mixed cryoglobulinemia
G Montagnino |
Springer Seminars in Immunopathology | 1988 |
Problems in the Rheumatic Diseases
RA Asherson, SH Morgan, GR Hughes |
1988 | |
Systemic Inflammatory Disease and the Eye
WJ Dinning |
Systemic Inflammatory Disease and the Eye | 1987 |
Cryoglobulinemia in autoimmune rheumatic diseases: Evidence of circulating monoclonal cryoglobulins in patients with primary Sjögren's syndrome
AG Tzioufas, MN Manoussakis, R Costello, M Silis, NM Papadopoulos, HM Moutsopoulos |
Arthritis & Rheumatism | 1986 |
Rheumatoid Arthritis with Pleural Effusion Includes a Subgroup with Autoimmune Features and HLA-B8, Dw3 Association
M Hakala, A Tiilikainen, R Hämeenkorpi, J Ilonen, S Jalava, P Ruuska, R Mäkitalo |
Scandinavian Journal of Rheumatology | 1986 |
Management of rheumatoid arthritis
CE Dugowson, BC Gilliland |
Disease-a-Month | 1986 |
Rheumatoid vasculitis: Experience with 13 patients and review of the literature
HA Schneider, RA Yonker, P Katz, S Longley, RS Panush |
Seminars in Arthritis and Rheumatism | 1985 |
Cryoglobulins in cases of rheumatoid arthritis.
Chattopadhya D, Ravindran B, Prakash K |
Rheumatology International | 1985 |
Clinical profiles of patients with antibodies to nuclear ribonucleoprotein
J Calderon, V Rodriguez-Valverde, SS Andrade, JL Riestra, J Gomez-Reyno |
Clinical Rheumatology | 1984 |
Rheumatoid Arthritis with severe Aortic lnsufficiency and Prolapse of the Mitral Valve
M Flores, J Agosti, C Damborenea, C Aguirre |
Scandinavian Journal of Rheumatology | 1984 |
Lyme disease—A review of the literature
PK Williamson, JJ Calabro |
Seminars in Arthritis and Rheumatism | 1984 |
Intravenous cyclophosphamide plus methylprednisolone in treatment of systemic rheumatoid vasculitis
DG Scott, PA Bacon |
The American Journal of Medicine | 1984 |
Néphropathies glomérulaires au cours de la polyarthrite rhumatoïde non traitée Revue de la littérature à propos de deux cas
D Clerc, JF Delfraissy, D Sallière, M Bisson, P Massias |
La Revue de Médecine Interne | 1984 |
Rheumatoid Arthritis: The Treatment Controversy
DH Goddard, RC Butler |
1984 | |
Differences in immunochemical characteristics of cryoglobulins in rheumatoid arthritis and systemic lupus erythematosus and their complement binding properties
CC Erhardt, P Mumford, RN Maini |
Annals of the rheumatic diseases | 1984 |
Spontaneous nasal septal perforation in patients with rheumatoid arthritis
JL Mathews, JR Ward, CO Samuelson, WP Knibbe |
Clinical Rheumatology | 1983 |
Rheumatoid vasculitis
DG Scott, PA Bacon |
Clinical Rheumatology | 1983 |
Rheumatoid vasculitis: diagnostic and therapeutic decisions
RS Panush, P Katz, S Longley, R Carter, J Love, H Stanley |
Clinical Rheumatology | 1983 |
POST PARTUM NEPHROTIC SYNDROME IN MIXED ESSENTIAL CRYOGLOBULINEMIA
GJ Goodman, PF Ryan, RA Sinclair |
Australian and New Zealand Journal of Medicine | 1983 |
Circulating Immune Complexes in Rheumatoid Arthritis with Extra-Articular Manifestations
H Jans, P Halberg, I Lorenzen |
Scandinavian Journal of Rheumatology | 1983 |
Correlation of antibody to rheumatoid arthritis associated nuclear antigen and immune complexes to disease activity in patients with rheumatoid arthritis
MA Alspaugh, D Rosenstock, JJ Biundo, RC Gupta |
Clinical & Experimental Immunology | 1983 |
IgG rheumatoid factors and anti-nuclear antibodies in rheumatoid vasculitis
FP Quismorio, T Beardmore, RL Kaufman, ES Mongan |
Clinical & Experimental Immunology | 1983 |
Dermatologic conditions reported in patients with rheumatoid arthritis
JL Jorizzo, JC Daniels |
Journal of the American Academy of Dermatology | 1983 |
Histamine-triggered localized vasculitis in patients with seropositive rheumatoid arthritis
JL Jorizzo, JC Daniels, P Apisarnthanarax, EB Gonzalez, T Cavallo |
Journal of the American Academy of Dermatology | 1983 |
Cutaneous Manifestations of Rheumatoid Arthritis
WL Sibbitt, RC Williams |
International Journal of Dermatology | 1982 |
Cutaneous and Systemic Manifestations of Auto-Immune Disorders
GV Gordon |
International Journal of Dermatology | 1982 |
Physiological aspects of circulating immune complexes in the normal population
CE Contreras, A Orozco, P Sánchez, G Ortega, NE Bianco |
Clinical & Experimental Immunology | 1982 |
Acute abdominal complications of systemic lupus erythematosus and polyarteritis nodosa
TM Zizic, JN Classen, MB Stevens |
The American Journal of Medicine | 1982 |
Plasma Exchange in Rheumatoid Vasculitis
DB Brubaker, A Winkelstein |
Vox Sanguinis | 1981 |
Characterization of a spontaneous disease of white leghorn chickens resembling progressive systemic sclerosis (scleroderma)
ME Gershwin, H Abplanalp, JJ Castles, RM Ikeda, J der Water, J Eklund, D Haynes |
Journal of Experimental Medicine | 1981 |
IgG rheumatoid factor, complement and immune complexes in rheumatoid synovitis and vasculitis: comparative and serial studies during cytotoxic therapy
DG Scott, PA Bacon, C Allen, CJ Elson, T Wallington |
Clinical & Experimental Immunology | 1981 |
Immunologic and clinical aspects of immune complex disease
RD Inman, NK Day |
The American Journal of Medicine | 1981 |
Nodular regenerative hyperplasia of the liver associated with macroglobulinemia
IR Wanless, LC Solt, P Kortan, JH Deck, GW Gardiner, EJ Prokipchuk |
The American Journal of Medicine | 1981 |
Evidence for defect of complement-mediated phagocytosis by monocytes from patients with rheumatoid arthritis and cutaneous vasculitis
NP Hurst, G Nuki |
BMJ : British Medical Journal | 1981 |
Granulocyte-Specific Antinuclear Antibodies
A Wilk |
Allergy | 1980 |
New clinical and immunological trends in cryoglobulinemia
F Dammacco, G Gnisci, F Silvestris, L Bonomo |
La Ricerca in Clinica e in Laboratorio | 1980 |
A clinical approach to systemic vasculitis
PT Fan, JA Davis, T Somer, L Kaplan, R Bluestone |
Seminars in Arthritis and Rheumatism | 1980 |
Immune complexes in human diseases: a review
AN Theofilopoulos, FJ Dixon |
The American Journal of Pathology | 1980 |
Granulocyte-Specific Antinuclear Antibodies.: Possible Significance for the Pathogenesis, Clinical Features and Diagnosis of Rheumatoid Arthritis
A Wilk |
Allergy | 1980 |
Mixed cryoglobulinemia: Clinical aspects and long-term follow-up of 40 patients
PD Gorevic, HJ Kassab, Y Levo, R Kohn, M Meltzer, P Prose, EC Franklin |
The American Journal of Medicine | 1980 |
Cutaneous vascular immunofluorescence in rheumatoid arthritis
RJ Rapoport, F Kozin, SE Mackel, RE Jordon |
The American Journal of Medicine | 1980 |
Ergebnisse der Inneren Medizin und Kinderheilkunde / Advances in Internal Medicine and Pediatrics
P Frick, GA von Harnack, GA Martini, A Prader, HP Wolff |
1980 | |
Survey of synovial fluid cryoprecipitates
CL Ludivico, AR Myers |
Annals of the rheumatic diseases | 1980 |
Vasculitis in Connective Tissue Diseases
MH Weisman, NJ Zvaifler |
Clinics in rheumatic diseases | 1980 |
Correlation of Serum and Cryoglobulin IgM with Activity, and Serum IgG with Remission
AC Steere, JA Hardin, S Ruddy, JG Mummaw, SE Malawista |
Arthritis & Rheumatism | 1979 |
Arthritis associated with jejunoileal bypass
M Zapanta, M Aldo-Benson, A Biegel, J Madura |
Arthritis & Rheumatism | 1979 |
Survey for immune complexes in disseminated gonococcal arthritis-dermatitis syndrome
CL Ludivico, AR Myers |
Arthritis & Rheumatism | 1979 |
Limited plasmapheresis in rheumatoid arthritis with vasculitis
JA Goldman, HL Casey, H Mcilwain, J Kirby, CH Wilson, SB Miller |
Arthritis & Rheumatism | 1979 |
Glomerulonephritis in rheumatoid arthritis
JA Davis, AH Cohen, R Weisbart, HE Paulus |
Arthritis & Rheumatism | 1979 |
The association of cryoglobulinaemia with nodules, vasculitis and fibrosing alveolitis in rheumatoid arthritis and their relationship to serum C1q binding activity and rheumatoid factor
CC Erhardt, P Mumford, RN Maini |
Clinical & Experimental Immunology | 1979 |
The role of IgM rheumatoid factor in experimental immune vasculitis
M Floyd, JT Tesar |
Clinical & Experimental Immunology | 1979 |
Cell Biology and Immunology of Leukocyte Function
MH Freedman |
Cell Biology and Immunology of Leukocyte Function | 1979 |
Lymphocyte reactivity of antisera to cryoproteins in systemic lupus erythematosus
JH Klippel, HG Bluestein, NJ Zvaifler |
Clinical Immunology and Immunopathology | 1979 |
Antibody-mediated suppression of antibody-dependent cytotoxic effector cell function
NJ Zvaifler, HG Bluestein |
Clinical Immunology and Immunopathology | 1979 |
Autoimmune manifestations of selective 7 S immunoglobulin deficiency of chickens
J Montero, ME Gershwin, J Eklund, H Abplanalp, K Erickson, L Tam, AA Benedict, RM Ikeda |
Clinical Immunology and Immunopathology | 1979 |
Studies on immune complexes in rheumatoid arthritis
T Nishimaki, K Kano, F Milgrom |
Arthritis & Rheumatism | 1978 |
Circulating Immune Complexes: Current Concepts of their Pathogenetic Role and Methods of Detection
RN Maini |
Australian and New Zealand Journal of Medicine | 1978 |
Complement-fixing material in ther sera of patients with rheumatoid arthritis
FC McDuffie, GG Hunder, RJ Clark |
Clinical & Experimental Immunology | 1978 |
Serum antibodies to fetal antigens in systemic lupus erythematosus and rheumatoid arthritis
FA Salinas, FP Quismorio, GJ Friou |
Clinical Immunology and Immunopathology | 1978 |
Rapid cryoglobulin screening: an aid to the clinician
AE Kalovidouris, RL Johnson |
Annals of the rheumatic diseases | 1978 |
Die Leber Bei Entzündlichen Rheumatischen Erkrankungen
R Rau |
1978 | |
Cryoglobulinaemia in Henoch-Schönlein purpura
M Garcia-Fuentes, C Chantler, DG Williams |
British medical journal | 1977 |
Echocardiographic assessment of cardiac structure and function in patients with rheumatoid arthritis
WJ MacDonald, MH Crawford, JH Klippel, NJ Zvaifler, RA O'Rourke |
The American Journal of Medicine | 1977 |
Systemic Complications of Rheumatoid Arthritis
JW Hollingsworth, RJ Saykaly |
Medical Clinics of North America | 1977 |
Rheumatoid Arthritis—General Features
BM Ansell, G Loewi |
Clinics in rheumatic diseases | 1977 |
Circulating and intra-articular immune complexes in patients with rheumatoid arthritis. Correlation of 125I-Clq binding activity with clinical and biological features of the disease
RH Zubler, U Nydegger, LH Perrin, K Fehr, J McCormick, PH Lambert, PA Miescher |
Journal of Clinical Investigation | 1976 |
Cryoimmunoglobulinemia in felty's syndrome
M Weisman, NJ Zvaifler |
Arthritis & Rheumatism | 1976 |
Rheumatoid vasculitis
D Glass, NA Soter, PH Schur |
Arthritis & Rheumatism | 1976 |