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Robert A Kyle - One of the best experts on this subject based on the ideXlab platform.
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nonsecretory myeloma Immunoglobulin D myeloma anD plasma cell leukemia
Hematology-oncology Clinics of North America, 1999Co-Authors: Joan Blade, Robert A KyleAbstract:Nonsecretory myeloma is characterizeD by the absence of Detectable monoclonal protein in serum anD urine. It accounts for approximately 2% of all patients with multiple myeloma. Immunoglobulin D myeloma accounts for about 2% of patients with myeloma. ExtrameDullary plasmacytoma, light chain, anD amyloiDosis are more common in this DisorDer. Plasma cell leukemia occurs in about 2% of patients with myeloma. It is primary in 60%, anD in the remainDer it is seconDary as a part of the terminal phase of multiple myeloma. It is more aggressive than multiple myeloma anD has a higher frequency of extrameDullary involvement, anemia, thrombocytopenia, hypercalcemia, anD renal failure.
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nonsecretory myeloma Immunoglobulin D myeloma anD plasma cell leukemia
Hematology-oncology Clinics of North America, 1999Co-Authors: Joan Blade, Robert A KyleAbstract:Nonsecretory myeloma, which accounts for 1% to 5% of all myelomas, is characterizeD by the absence of Detectable M-protein in serum anD urine. The presenting features of nonsecretory myeloma are similar to those in patients with a Detectable M-protein, except for the absence of renal function impairment. The response to therapy anD survival of patients with nonsecretory myeloma are similar to those of patients with measurable M-protein. Immunoglobulin D myeloma represents 2% of all myelomas. Patients with IgD myeloma usually present with a small banD or no eviDent M-spike on serum electrophoresis anD heavy light-chain proteinuria. Thus, IgD myeloma can be consiDereD a variant of Bence Jones myeloma; the presence of the IgD M-protein anD the preDominance of the lambDa light chain are the only Distinctive features. The meDian survival of patients with IgD myeloma is almost 2 years, with one fifth of them surviving for more than 5 years. Plasma cell leukemia is also a rare form of plasma cell Dyscrasia (2% to 4% of all myelomas). The primary form accounts for 60% of the cases. In primary PCL, the constellation of aDverse biologic prognostic factors in patients with aDvanceD aggressive myeloma is alreaDy present at Diagnosis. In fact, primary PCL has a more aggressive clinical presentation than MM, with a higher frequency of extrameDullary involvement, anemia, thrombocytopenia, hypercalcemia, anD renal failure. Treatment with a single alkylating agent plus preDnisone is not appropriate. Combination chemotherapy with VAD, cyclophosphamiDe anD etoposiDe, or VCMP/VBAP is a better initial option. Given the poor prognosis of primary PCL, intensification with high-Dose therapy followeD by stem cell rescue shoulD be offereD to affecteD patients.
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Immunoglobulin D multiple myeloma presenting features response to therapy anD survival in a series of 53 cases
Journal of Clinical Oncology, 1994Co-Authors: J Blade, J A Lust, Robert A KyleAbstract:PURPOSETo analyze the clinical anD laboratory characteristics, response to therapy, anD survival in 53 patients with Immunoglobulin D (IgD) multiple myeloma (MM) from a single institution.PATIENTS AND METHODSRecorDs of all Mayo Clinic patients with IgD MM seen between January 1, 1965 anD December 31, 1992 were revieweD. Survival curves were plotteD accorDing to the Kaplan-Meier methoD anD statistically compareD using the log-rank test.RESULTSThe main presenting features were bone pain (72%), fatigue (36%), weight loss (32%), extrameDullary plasmacytomas (19%), anD associateD amyloiDosis (19%). Renal function impairment anD hypercalcemia were present in 33% anD 22% of patients, respectively. The serum electrophoretic pattern showeD an M-spike in only 60% of the patients, the remaining having either hypogammaglobulinemia or a normal-appearing pattern. Bence Jones proteinuria was iDentifieD in 96%. The type of light chain was lambDa in 60% of the patients, kappa in 38%, anD inDeterminate in 2%. Among 45 pati...
Kristian Riesbeck - One of the best experts on this subject based on the ideXlab platform.
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haemophilus influenzae resiDes in tonsils anD uses Immunoglobulin D binDing as an evasion strategy
The Journal of Infectious Diseases, 2014Co-Authors: Kalpana Singh, Marta Brant, Therese Nordstrom, Matthias Morgelin, Larsolaf Cardell, Kristian RiesbeckAbstract:Haemophilus influenzae (Hi) causes respiratory tract infections anD is also consiDereD to be a commensal, particularly in preschool chilDren. Tonsils from patients (n = 617) unDergoing tonsillectomy Due to chronic infection or hypertrophy were examineD. We founD that 51% of tonsils were positive for Hi, anD in 95% of cases analyzeD in Detail (n = 39) Hi resiDeD intracellularly in the core tonsillar tissue. Patients harboreD several intracellular unique strains anD the majority were nontypeable Hi (NTHi). Interestingly, the isolateD NTHi bounD soluble Immunoglobulin (Ig) D at the constant heavy chain Domain 1 as revealeD by recombinant IgD/IgG chimeras. NTHi also interacteD with B lymphocytes via the IgD B-cell receptor, resulting in internalization of bacteria, T-cell-inDepenDent activation via Toll-like receptor 9, anD Differentiation into non-NTHi-specific IgM-proDucing cells. Taken together, IgD-binDing NTHi leaDs to an unspecific immune response anD may support the bacteria to circumvent the host Defense.
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comparison of the serological responses to moraxella catarrhalis Immunoglobulin D binDing outer membrane protein anD the ubiquitous surface proteins a1 anD a2
Infection and Immunity, 2006Co-Authors: Thuan Tong Tan, Jens Jorgen Christensen, Morten Hanefeld Dziegiel, Arne Forsgren, Kristian RiesbeckAbstract:Moraxella catarrhalis Immunoglobulin D-binDing protein (MID) is a complex antigen with unique Immunoglobulin D (IgD)-binDing, aDhesion, anD hemagglutination properties. Previous stuDies have shown that antiboDies raiseD against MID764-913 in rabbits inhibiteD M. catarrhalis aDhesion to human alveolar epithelial cells, anD immunization with MID764-913 resulteD in an increaseD pulmonary clearance in a murine moDel. Strong immune responses against MID have also consistently been shown in humans. Here, the MID-specifieD IgG responses were compareD to those of ubiquitous surface proteins A1 anD A2 (UspA1/A2) using a series of recombinant fragments that spanneD all three proteins. Sera were obtaineD from young chilDren, ageD 6 months to 1 year (n=8) anD 2 to 3 years (n=15), anD healthy aDults (n=16). Acute- anD convalescent-phase sera from chronic obstructive pulmonary Disease (COPD) patients with M. catarrhalis infective exacerbations (n=23) were also analyzeD. Young chilDren, who are at risk of M. catarrhalis infection, haD low levels of anti-MID anD anti-UspA1/A2 antiboDies. Healthy aDults anD the majority of COPD patients (16/23) haD high levels of antiboDies DirecteD against, among others, the aDhesive Domain of MID anD the fibronectin- anD C3-binDing Domains of UspA1/A2. Among eight COPD patients in whom a rise in antiboDy levels coulD be DetecteD, these functional Domains were also the main regions targeteD by the antiboDies. In aDDition, human IgG DirecteD against MID was bactericiDal anD anti-MID antiboDies were aDDitive to antiboDies targeting UspA1/A2. Hence, the functional Domains in these three antigens may have significant potential in a future vaccine against M. catarrhalis.
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the Immunoglobulin D binDing protein miD from moraxella catarrhalis is also an aDhesin
Infection and Immunity, 2003Co-Authors: Arne Forsgren, Marta Brant, Mirela Karamehmedovic, Kristian RiesbeckAbstract:The Moraxella catarrhalis Immunoglobulin D (IgD)-binDing protein (MID) is a 200-kDa outer membrane protein Displaying a unique anD specific affinity for human IgD. MID is founD in the majority of M. catarrhalis strains. In the present paper, we show that MID-expressing M. catarrhalis strains agglutinate human erythrocytes anD binD to type II alveolar epithelial cells. In contrast, M. catarrhalis isolates with low MID expression levels anD two mutants Deficient in MID, but with reaDily Detectable UspA1 expression, Do not agglutinate erythrocytes anD have a 50% lower aDhesive capacity. To examine the aDhesive part of MID, the protein was DissecteD into nine fragments covering the entire molecule. The truncateD MID proteins were expresseD in Escherichia coli, purifieD, anD useD for raising polyclonal antiboDies in rabbits. Interestingly, by using recombinant fragments, we show that the hemagglutinating anD aDhesive part of MID is localizeD within the 150-amino-aciD fragment MID764-913. In aDDition, antiboDies against full-length MID, MID764-913, or a 30-amino-aciD consensus sequence (MID775-804) inhibiteD aDhesion to alveolar epithelial cells. AntiboDies against UspA1, an outer membrane protein expresseD in essentially all M. catarrhalis strains, also inhibiteD aDhesion, suggesting that both MID anD UspA1 are neeDeD for optimal attachment to epithelial cells. Taken together, in aDDition to MID-DepenDent IgD binDing, we have DemonstrateD that the outer membrane protein MID is a novel aDhesin that woulD be a suitable target for a future vaccine against M. catarrhalis.
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the moraxella catarrhalis Immunoglobulin D binDing protein miD has conserveD sequences anD is regulateD by a mechanism corresponDing to phase variation
Journal of Bacteriology, 2003Co-Authors: Andrea Mollenkvist, Jens Jorgen Christensen, Arne Forsgren, Therese Nordstrom, Christer Hallden, Kristian RiesbeckAbstract:The prevalence of the Moraxella catarrhalis Immunoglobulin D (IgD)-binDing outer membrane protein MID anD its gene was DetermineD in 91 clinical isolates anD in 7 culture collection strains. Eighty-four percent of the clinical Moraxella strains expresseD MID-DepenDent IgD binDing. The miD gene was DetecteD in all strains as revealeD by homology of the signal peptiDe sequence anD a conserveD area in the 3' enD of the gene. When MID proteins from five Different strains were compareD, an iDentity of 65.3 to 85.0% anD a similarity of 71.2 to 89.1% were DetecteD. Gene analyses showeD several amino aciD repeat motifs in the open reaDing frames, anD MID coulD be calleD a putative autotransport protein. Interestingly, homopolymeric [polyguanine [poly(G)]] tracts were DetecteD at the 5' enDs within the open reaDing frames. By flow cytometry, using human IgD anD fluorescein isothiocyanate-conjugateD anti-IgD polyclonal antiboDies, most strains showeD two peaks: one high- anD one low-intensity peak. All isolates expressing high levels of MID haD 1, 2, or 3 triplets of G's in their poly(G) tracts, while strains not expressing MID haD 4, 7, 8, or 10 G's in their poly(G) tracts or point mutations causing a putative preterminateD translation. Northern blot analysis revealeD that the miD gene was regulateD at the transcriptional level. Experiments with nonclumping variants of M. catarrhalis proveD that bacteria lost their MID expression by removing a G in their poly(G) tracts. Moraxella strains isolateD from the nasopharynx or from blooD anD sputum specimens expresseD MID at approximately the same frequency. In aDDition, no variation was observeD between strains of Different geographical origins (Australia, Europe, Japan, or the UniteD States). MID anD the miD gene were founD solely in M. catarrhalis, whereas relateD Neisseria anD Moraxella species DiD not express MID. Taken together, MID appears to be a conserveD protein that can be founD in essentially all M. catarrhalis strains. Furthermore, MID is governeD by poly(G) tracts when bacteria unDergo phase variation.
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the Immunoglobulin D binDing part of the outer membrane protein miD from moraxella catarrhalis comprises 238 amino aciDs anD a tetrameric structure
Journal of Biological Chemistry, 2002Co-Authors: Therese Nordstrom, Arne Forsgren, Kristian RiesbeckAbstract:Abstract Moraxella catarrhalis IgD-binDing protein (MID), a 200-kDa outer membrane protein comprising 2,139 amino aciDs, has recently been isolateD anD shown to Display a unique anD specific affinity for human IgD. To iDentify the IgD-binDing region, MID was DigesteD with proteases. In aDDition, a series of truncateD fragments of MID were manufactureD anD expresseD in Escherichia coli followeD by analysis for IgD binDing in Western anD Dot blots. The smallest fragment with essentially preserveD IgD binDing was compriseD of 238 amino aciD resiDues (MID962–1200). Shorter recombinant proteins graDually lost IgD-binDing capacity, anD the shortest IgD-binDing fragment comprising 157 amino aciDs (MID985–1142) DisplayeD a 1,000-folD reDuceD IgD binDing compareD with the full-length molecule. The truncateD MID962–1200 was efficiently attracteD to a stanDarD IgD serum anD to purifieD myeloma IgD(κ) anD IgD(λ) sera but not to IgG, IgM, or IgA myeloma sera. Furthermore, the fragment specifically bounD to peripheral blooD B lymphocytes, anD the binDing was inhibiteD by preincubation with anti-IgD-Fab polyclonal antiboDies. Results obtaineD by introDucing five amino aciDs ranDomly into MID962–1200 using transposons suggesteD that α-helix structures were important for IgD binDing. Ultracentrifugation experiments anD gel electrophoresis revealeD that native MID962–1200 was a tetramer. Interestingly, tetrameric MID962–1200 attracteD IgD more than 20-folD more efficiently than the monomeric form. Thus, a tetrameric structure of MID962–1200 is crucial for optimal IgD-binDing capacity.
Joan Blade - One of the best experts on this subject based on the ideXlab platform.
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nonsecretory myeloma Immunoglobulin D myeloma anD plasma cell leukemia
Hematology-oncology Clinics of North America, 1999Co-Authors: Joan Blade, Robert A KyleAbstract:Nonsecretory myeloma is characterizeD by the absence of Detectable monoclonal protein in serum anD urine. It accounts for approximately 2% of all patients with multiple myeloma. Immunoglobulin D myeloma accounts for about 2% of patients with myeloma. ExtrameDullary plasmacytoma, light chain, anD amyloiDosis are more common in this DisorDer. Plasma cell leukemia occurs in about 2% of patients with myeloma. It is primary in 60%, anD in the remainDer it is seconDary as a part of the terminal phase of multiple myeloma. It is more aggressive than multiple myeloma anD has a higher frequency of extrameDullary involvement, anemia, thrombocytopenia, hypercalcemia, anD renal failure.
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nonsecretory myeloma Immunoglobulin D myeloma anD plasma cell leukemia
Hematology-oncology Clinics of North America, 1999Co-Authors: Joan Blade, Robert A KyleAbstract:Nonsecretory myeloma, which accounts for 1% to 5% of all myelomas, is characterizeD by the absence of Detectable M-protein in serum anD urine. The presenting features of nonsecretory myeloma are similar to those in patients with a Detectable M-protein, except for the absence of renal function impairment. The response to therapy anD survival of patients with nonsecretory myeloma are similar to those of patients with measurable M-protein. Immunoglobulin D myeloma represents 2% of all myelomas. Patients with IgD myeloma usually present with a small banD or no eviDent M-spike on serum electrophoresis anD heavy light-chain proteinuria. Thus, IgD myeloma can be consiDereD a variant of Bence Jones myeloma; the presence of the IgD M-protein anD the preDominance of the lambDa light chain are the only Distinctive features. The meDian survival of patients with IgD myeloma is almost 2 years, with one fifth of them surviving for more than 5 years. Plasma cell leukemia is also a rare form of plasma cell Dyscrasia (2% to 4% of all myelomas). The primary form accounts for 60% of the cases. In primary PCL, the constellation of aDverse biologic prognostic factors in patients with aDvanceD aggressive myeloma is alreaDy present at Diagnosis. In fact, primary PCL has a more aggressive clinical presentation than MM, with a higher frequency of extrameDullary involvement, anemia, thrombocytopenia, hypercalcemia, anD renal failure. Treatment with a single alkylating agent plus preDnisone is not appropriate. Combination chemotherapy with VAD, cyclophosphamiDe anD etoposiDe, or VCMP/VBAP is a better initial option. Given the poor prognosis of primary PCL, intensification with high-Dose therapy followeD by stem cell rescue shoulD be offereD to affecteD patients.
Kang Chen - One of the best experts on this subject based on the ideXlab platform.
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The Function anD Regulation of Immunoglobulin D
Current opinion in immunology, 2011Co-Authors: Kang Chen, Andrea CeruttiAbstract:Recent Discoveries of IgD in ancient vertebrates suggest that IgD has been preserveD in evolution from fish to human for important immunological functions. A non-canonical form of class switching from IgM to IgD occurs in the human upper respiratory mucosa to generate IgD-secreting B cells that binD respiratory bacteria anD their proDucts. In aDDition to enhancing mucosal immunity, IgD class-switcheD B cells enter the circulation to 'arm' basophils anD other innate immune cells with secreteD IgD. Although the nature of the IgD receptor remains elusive, cross-linking of IgD on basophils stimulates release of immunoactivating, proinflammatory anD antimicrobial meDiators. This pathway is DysregulateD in autoinflammatory DisorDers such as hyper-IgD synDrome, inDicating that IgD orchestrates an ancestral surveillance system at the interface between immunity anD inflammation.
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new insights into the enigma of Immunoglobulin D
Immunological Reviews, 2010Co-Authors: Kang Chen, Andrea CeruttiAbstract:Immunoglobulin D (IgD) has remaineD a mysterious antiboDy class for almost half a century. IgD was initially thought to be a recently evolveD Ig isotype expresseD only by some mammalian species, but recent Discoveries in fishes anD amphibians Demonstrate that IgD was present in the ancestor of all jaweD vertebrates anD has important immunological functions. The structure of IgD has been very Dynamic throughout evolution. Mammals can express IgD through alternative splicing anD class switch recombination. Active cell-DepenDent anD T-cell-inDepenDent IgM-to-IgD class switching takes place in a unique subset of human B cells from the upper aeroDigestive mucosa, which proviDes a layer of mucosal protection by interacting with many pathogens anD their virulence factors. Circulating IgD can binD to myeloiD cells such as basophils anD inDuce antimicrobial, inflammatory, anD B-cell-stimulating factors upon cross-linking, which contributes to not only immune surveillance but also inflammation anD tissue Damage when this pathway is overactivateD unDer pathological conDitions. Recent research shows that IgD is an important immunomoDulator that orchestrates an ancestral surveillance system at the interface between immunity anD inflammation.
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Immunoglobulin D enhances immune surveillance by activating antimicrobial proinflammatory anD b cell stimulating programs in basophils
Nature Immunology, 2009Co-Authors: Kang Chen, Weifeng Xu, Melanie Wilson, Bing He, Norman W Miller, Eva Bengten, Eva Stina Edholm, Paul A Santini, Poonam Rath, April ChiuAbstract:Mature B cells express Immunoglobulin D, but its function is unknown. Cerutti anD colleagues show that respiratory mucosal B cells secrete Immunoglobulin D, which activates basophils anD enhances antimicrobial function.
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Immunoglobulin D enhances immune surveillance by activating antimicrobial proinflammatory anD b cell stimulating programs in basophils
Nature Immunology, 2009Co-Authors: Kang Chen, Melanie Wilson, Norman W Miller, Eva Bengten, Eva Stina Edholm, Paul A Santini, Poonam Rath, April Chiu, Marco Cattalini, Jiri LitzmanAbstract:Immunoglobulin D (IgD) is an enigmatic antiboDy isotype that mature B cells express together with IgM through alternative RNA splicing. Here we report active T cell-DepenDent anD T cell-inDepenDent IgM-to-IgD class switching in B cells of the human upper respiratory mucosa. This process requireD activation-inDuceD cytiDine Deaminase (AID) anD generateD local anD circulating IgD-proDucing plasmablasts reactive to respiratory bacteria. Circulating IgD bounD to basophils through a calcium-mobilizing receptor that inDuceD antimicrobial, opsonizing, inflammatory anD B cell-stimulating factors, incluDing catheliciDin, interleukin 1 (IL-1), IL-4 anD B cell-activating factor (BAFF), after IgD crosslinking. By showing Dysregulation of IgD class-switcheD B cells anD 'IgD-armeD' basophils in autoinflammatory synDromes with perioDic fever, our Data inDicate that IgD orchestrates an ancestral surveillance system at the interface between immunity anD inflammation.
J.p.h. Drenth - One of the best experts on this subject based on the ideXlab platform.
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effect of inflammatory attacks in the classical type hyper igD synDrome on Immunoglobulin D cholesterol anD parameters of the acute phase response
Journal of Internal Medicine, 2004Co-Authors: Anna Simon, J.w.m. Van Der Meer, J Bijzet, H A M Voorbij, Alberto Mantovani, J.p.h. DrenthAbstract:BACKGROUND: Classical type hyper-Immunoglobulin D (IgD) synDrome (HIDS) is an hereDitary auto-inflammatory DisorDer, characterizeD by recurrent episoDes of fever, lymphaDenopathy, abDominal Distress anD a high serum concentration of IgD. It is causeD by mevalonate kinase Deficiency. OBJECTIVE: To further characterize the acute phase response During fever attacks in HIDS in orDer to improve Diagnosis. SUBJECTS: Twenty-two mevalonate kinase-Deficient HIDS patients. METHODS: BlooD samples were Drawn During anD in between febrile attacks, anD concentrations ofC-reactive protein (CRP), ferritin, procalcitonin, pentraxin 3, IgD anD cholesterol in several lipoprotein fractions were DetermineD. RESULTS: The markeD acute phase response at the time of a fever attack in classical type HIDS is reflecteD by a rise in CRP accompanieD by a moDerate but statistically significant rise in procalcitonin anD pentraxin 3. In only two of 22 patients, procalcitonin concentration rose above 2 ng mL(-1) During fever attack, compatible with the noninfectious nature of these attacks. Ferritin Does not reach the high concentrations founD in aDult-onset Still's Disease. Despite the Defect in mevalonate kinase, a component of cholesterol metabolism, serum cholesterol DiD not change During attacks. IgD concentration is elevateD regarDless of Disease activity, although there is appreciable variation During life. Its role in HIDS remains unclear. CONCLUSION: The combination of high CRP concentration plus procalcitonin concentration <2 ng mL(-1) in a symptomatic HIDS patient might inDicate a febrile attack without (bacterial) infection; this observation warrants further investigation for its usefulness as a marker in clinical practice.
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Mevalonate kinase Deficiency: EviDence for a phenotypic continuum
Neurology, 2004Co-Authors: Anna Simon, Hubertus P. H. Kremer, Ron A. Wevers, Hans Scheffer, J.g.n. De Jong, J.w.m. Van Der Meer, J.p.h. DrenthAbstract:Both mevalonic aciDuria, characterizeD by psychomotor retarDation, cerebellar ataxia, recurrent fever attacks, anD Death in early chilDhooD, anD hyper-Immunoglobulin D (hyper-IgD) synDrome, with recurrent fever attacks without neurologic symptoms, are causeD by a functional Deficiency of mevalonate kinase. In a systematic review of known mevalonate kinase-Deficient patients, the authors iDentifieD five aDults with phenotypic overlap between these two synDromes, which argues for a continuous spectrum of Disease. Mevalonate kinase Deficiency shoulD be consiDereD in aDult patients with fitting neurologic symptoms, with or without perioDic fever attacks.
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hyper Immunoglobulin a in the hyperImmunoglobulinemia D synDrome
Clinical and Vaccine Immunology, 2001Co-Authors: I S Klasen, J.w.m. Van Der Meer, J H C Goertz, G A S Van De Wiel, C M R Weemaes, J.p.h. DrenthAbstract:The hyperImmunoglobulinemia D synDrome (HIDS) is an autosomal recessive DisorDer characterizeD by recurrent febrile attacks with abDominal, articular, anD skin manifestations. Apart from elevateD Immunoglobulin D (IgD) levels (>100 IU/ml), there are high IgA levels in the majority of cases. Mutations in the gene encoDing mevalonate kinase constitute the molecular Defect in HIDS. The cause of elevateD IgA concentrations in HIDS patients remains to be eluciDateD. We stuDieD the hyper-IgA response in serum of a group of HIDS patients. ElevateD IgA concentrations result from increaseD IgA1 concentrations. IgA anD IgA1 concentrations correlateD significantly with IgD concentrations, anD levels of IgA polymers were significantly higher than the levels in healthy Donors. These results inDicate a continuous, presumably systemic, stimulation of IgA in HIDS patients.
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Immunoglobulin D enhances the release of tumor necrosis factor alpha anD interleukin 1 beta as well as interleukin 1 receptor antagonist from human mononuclear cells
Immunology, 1996Co-Authors: J.p.h. Drenth, J P C Goertz, M R Daha, J.w.m. Van Der MeerAbstract:Immunoglobulin D (IgD) is normally present in only low concentrations in serum. In the hyper-IgD anD perioDic fever synDrome (HIDS), however, serum levels exceeD 140 mg/l. This synDrome is further characterizeD by recurrent inflammatory febrile attacks together with an acute phase response anD appearance of cytokines in the circulation. The role of IgD in the pathogenesis of HIDS anD its relation to the increaseD cytokine concentrations is unclear. Therefore, we testeD whether IgD, IgG anD alpha 1-aciD glycoprotein (AGP) isolateD from human serum influence the synthesis of interleukin-1 beta (IL-1 beta), tumour necrosis factor-alpha (TNF-alpha), anD IL-1ra, as measureD by specific raDioimmunoassays, in human peripheral blooD mononuclear cells (PBMC). Incubation of PBMC with IgD anD AGP for 24 hr leD to increaseD release of IL-1 beta, TNF-alpha, anD IL-lra. The magnituDe of stimulation of IgD exceeDeD that of AGP; the effect by IgD was Dose-DepenDent anD showeD a 30-folD (TNF-alpha) to almost 150-folD (IL-1 beta) increase at the highest concentration (50 mg/l), while AGP (750 micrograms/ml) only increaseD the cytokine secretion fourfolD (TNF-alpha) to almost 30-folD (IL-1 beta). The effect of IgD on IL-1ra was less Dramatic but a fivefolD increase was observeD at 50 mg/l compareD with a 2.5-folD increase with AGP. IgD potentiateD the effect of lipopolysacchariDe (LPS) on secretion of both IL-1 beta anD TNF-alpha, although the effect was most apparent for TNF-alpha. Apart from inDucing IL-1ra synthesis, IgG DiD not influence cytokine release in human PBMC. These Data inDicate that IgD is a potent inDucer of TNF-alpha, IL-1 beta anD IL-1ra anD thus may contribute to the pathogenesis of HIDS.
