AIM:To investigate the expression of interferon regulatory factors(IRFs)in peripheral blood mononuclear cells(PBMCs)of patients with Sjögren’s syndrome-related dry eye(SSDE)and to explore their correlation with ...AIM:To investigate the expression of interferon regulatory factors(IRFs)in peripheral blood mononuclear cells(PBMCs)of patients with Sjögren’s syndrome-related dry eye(SSDE)and to explore their correlation with clinical features,dendritic cell activation,and serological indicators.METHODS:A total of 53 SSDE patients and 62 non-Sjögren’s syndrome dry eye(NSSDE)patients were enrolled.Demographic and clinical data were collected,and comprehensive ophthalmic examinations were performed,including the ocular surface disease index(OSDI)questionnaires,Schirmer I test(SIT),tear break-up time(TBUT),corneal fluorescein staining score(CFS),and in vivo confocal microscopy(IVCM).PBMCs were isolated,and IRFs expression levels were analyzed using Western blotting(WB)and quantitative real-time polymerase chain reaction(qRT-PCR).Serological indicators,including antinuclear antibodies(ANA)and anti-Ro60,anti-Ro52,and anti-La autoantibodies,were detected.Statistical analyses evaluated correlations between IRFs expression and clinical parameters.RESULTS:Compared to NSSDE,the relative mRNA and protein expression of the IRF-8 was significantly upregulated in patients with SSDE(P<0.001),whereas no significant differences were observed in IRF-1,IRF-3,IRF-5,and IRF-7(P=0.12,P=0.10,P=0.66,P=0.96).Correlation analysis revealed that IRF-8 expression was positively associated with CFS and OSDI scores(r=0.57,r=0.38,both P<0.05).Moreover,IRF-8 expression correlated with corneal dendritic cell(DC)density and size,and the number of dendrites(r=0.43,r=0.40,r=0.65,all P<0.05).IRF-8 expression was significantly elevated in patients positive for anti-Ro60,anti-Ro52 and anti-La autoantibodies(P<0.05).CONCLUSION:In SSDE,IRF-8 is upregulated and associated with clinical features,DC activation,and serological indicators.These findings suggest that IRF-8 plays a critical role in SSDE pathogenesis and may serve as a potential therapeutic target for diagnosis and treatment.展开更多
Tricellulin,a key tricellular tight junction(TJ)protein,is essential for maintaining the barrier integrity of acinar epithelia against macromolecular passage in salivary glands.This study aims to explore the role and ...Tricellulin,a key tricellular tight junction(TJ)protein,is essential for maintaining the barrier integrity of acinar epithelia against macromolecular passage in salivary glands.This study aims to explore the role and regulatory mechanism of tricellulin in the development of salivary gland hypofunction in Sjögren’s syndrome(SS).Employing a multifaceted approach involving patient biopsies,non-obese diabetic(NOD)mice as a SS model,salivary gland acinar cell-specific tricellulin conditional knockout(TricCKO)mice,and IFN-γ-stimulated salivary gland epithelial cells,we investigated the role of tricellulin in SS-related hyposalivation.Our data revealed diminished levels of tricellulin in salivary glands of SS patients.Similarly,NOD mice displayed a reduction in tricellulin expression from the onset of the disease,concomitant with hyposecretion and an increase in salivary albumin content.Consistent with these findings,TricCKO mice exhibited both hyposecretion and leakage of macromolecular tracers when compared to control animals.Mechanistically,the JAK/STAT1/miR-145 axis was identified as mediating the IFN-γ-induced downregulation of tricellulin.Treatment with AT1001,a TJ sealer,ameliorated epithelial barrier dysfunction,restored tricellulin expression,and consequently alleviated hyposalivation in NOD mice.Importantly,treatment with miR-145 antagomir to specifically recover the expression of tricellulin in NOD mice significantly alleviated hyposalivation and macromolecular leakage.Collectively,we identified that tricellulin deficiency in salivary glands contributed to hyposalivation in SS.Our findings highlight tricellulin as a potential therapeutic target for hyposecretion,particularly in the context of reinforcing epithelial barrier function through preventing leakage of macromolecules in salivary glands.展开更多
Introduction: Glomerular damage during Gougerot-Sjgren syndrome is much rarer than interstitial damage, and is essentially extra-membranous and membrano-proliferative glomerulonephritis. Observation: We report the cas...Introduction: Glomerular damage during Gougerot-Sjgren syndrome is much rarer than interstitial damage, and is essentially extra-membranous and membrano-proliferative glomerulonephritis. Observation: We report the case of a 44-year-old woman with primary Sjgrens syndrome, confirmed by clinical dryness syndrome, positive anti-SSA and anti-SSB antibodies, and a salivary gland biopsy revealing grade 4 lymphocytic sialadenitis according to CHISHOLMs classification. Later, the patient developed nephrotic syndrome, along with hypertension. Renal function remained normal with a creatinine level of 9.3 mg/l, and hematuria was absent. Only antinuclear antibodies tested positive, while anti-PLA2R antibodies were negative. A renal biopsy was performed, which was complicated on the same day by hemodynamic instability with hematuria. Renal CT scan with contrast injection revealed a posterior perirenal hematoma without contrast extravasation. Additionally, bilateral renal vein thrombosis was incidentally discovered, suggesting extramembranous glomerulonephritis. The patients hemodynamic status stabilized after fluid resuscitation with isotonic saline solution (0.9%), without the need for blood transfusion. Renal biopsy confirmed extramembranous glomerulonephritis with interstitial fibrosis and minimal tubular atrophy. The initial etiological assessment was negative. The patient was started on oral corticosteroids, angiotensin-converting enzyme inhibitors, and therapeutic anticoagulation for renal vein thrombosis. The patients condition improved, with the disappearance of the syndrome and spontaneous regression of the hematoma. Discussion: The association of nephrotic syndrome and renal vein thrombosis primarily suggests glomerulopathy, in particular extra-membranous glomerulonephritis. Sjgrens syndrome can be associated with extra-membranous glomerulonephritis without being its direct cause. Like, it is possible that it is a cause of glomerulonephritis, essentially extra membranous and membrano-proliferative. Conclusion: Sjgrens syndrome is generally underestimated cause of glomerulonephritis, which should be considered in cases of extra-membranous glomerulonephritis.展开更多
BACKGROUND Celiac disease(CD)is a systemic,chronic immune-mediated disease triggered by gluten ingestion in genetically-susceptible individuals,with a prevalence of 1%worldwide.Sjogren's syndrome(SS)is also a syst...BACKGROUND Celiac disease(CD)is a systemic,chronic immune-mediated disease triggered by gluten ingestion in genetically-susceptible individuals,with a prevalence of 1%worldwide.Sjogren's syndrome(SS)is also a systemic autoimmune disease,mainly characterized by ocular and oral sicca symptoms and signs.Sharing a common genetic background,CD and SS are known associated autoimmune diseases,but currently available guidelines are not reporting it.CASE SUMMARY We report the case of a 39-year-old woman,who was in the care of her rheumatologist for 2 years with SS.On routine follow-up she was found to have iron deficiency,without anemia.She had no gastrointestinal complaints and denied any obvious source of blood loss.IgA tissue transglutaminase antibodies were positive and endoscopy with duodenal biopsies revealed crypt hyperplasia and villous atrophy.A diagnosis of CD was set and gluten-free diet was recommended.CONCLUSION We present a review of existing data in the literature regarding the association of the two diseases,summarizing prevalence studies of CD in SS patients and the other way around.Screening recommendations and future research perspectives are also discussed,highlighting clinically relevant unanswered questions with respect to the association of CD with SS.展开更多
BACKGROUND Although the presentations of Sjögren’s syndrome(SS)are variable,ranging from mild dryness to wider systemic involvement,ranulas as early clinical signs were scarcely reported.Here,we present an adult...BACKGROUND Although the presentations of Sjögren’s syndrome(SS)are variable,ranging from mild dryness to wider systemic involvement,ranulas as early clinical signs were scarcely reported.Here,we present an adult patient with SS,who developed a unilateral simple ranula and was diagnosed primary SS 3 years later.We also provide a review of cases of SS and ranulas from 1980 to 2020.CASE SUMMARY A 22-year-old girl was found to have a left painless floor-of-mouth lesion 3 years ago,without obvious trauma or inducement.The diagnosis of a unilateral(left)simple ranula was made,and the ranula was surgically treated.Within 3 years after the ranula surgery,she developed acute lymphadenectasis in unilateral parotid twice without inducement,and ultrasonic examination revealed diffuse lesions in bilateral parotids and submandibular glands,which strongly suggested SS.Serologic tests and the unstimulated whole saliva flow rate confirmed the SS diagnosis.CONCLUSION Our study underlines that ranulas are early clinical signs of SS.As early diagnosis and early intervention of SS are important to obtain better outcomes,our findings underline the need for histopathological test after sublingual adenectomy and imaging detection of exocrine glands for the patients with ranulas.展开更多
BACKGROUND Primary Sjögren's syndrome(pSS)concomitant with autoimmune hemolytic anemia(AIHA)but without eye and mouth dryness is exceedingly rare.Iguratimod(IGU)has been widely used in the treatment of pSS.Ho...BACKGROUND Primary Sjögren's syndrome(pSS)concomitant with autoimmune hemolytic anemia(AIHA)but without eye and mouth dryness is exceedingly rare.Iguratimod(IGU)has been widely used in the treatment of pSS.However,there are few reports about the application of IGU in pSS concomitant with AIHA.CASE SUMMARY Here,we present the case of a patient with pSS concomitant with AIHA but without eye and mouth dryness.The patient was initially diagnosed with hyperplastic anemia and AIHA while pSS was missed,and was finally diagnosed with pSS concomitant with AIHA.The patient was treated with IGU along with prednisone and hydroxychloroquine,and her hemoglobin,reticulocytes and IgG returned to normal levels.CONCLUSION IGU was effective for and well tolerated by our patient with pSS concomitant with AIHA,and may be a promising therapy for the treatment of this disease.展开更多
Introduction: Sjögren’s syndrome is an autoimmune epithelitis with various extraglandular signs, among which are neurological, with a variable frequency according to studies. We report three cases of periphe...Introduction: Sjögren’s syndrome is an autoimmune epithelitis with various extraglandular signs, among which are neurological, with a variable frequency according to studies. We report three cases of peripheral neuropathy revealing Gougerot-Sjögren’s syndrome, collected in the Neurology Department of the Fann University Hospital in Dakar (Senegal). Observations: The first patient, aged 48 years, presented with a length-dependent sensitivomotor polyneuropathy associated with retrobulbar optic neuritis, with dry eyes and dry mouth noticed by the patient for several years. The second patient, aged 28 years, was admitted to the hospital with chronic generalized paresthesia in the context of xerostomia and xerophthalmia. The results of the clinical examination and the electroeneuromyogram were in favour of pure sensory neuronopathy. The third patient was 32 years old female, with a history of thyroidectomy and acute inflammatory demyelinating polyneuropathy (AIDP), who was seen for acute ascending flaccid tetraplegia with facial diplegia, preceded by diffuse paresthesia. The diagnosis of recurrence of acute demyelinating polyradiculonueropathy was retained in view of the rapidly increasing character of the deficit, the hyperproteinorachy at the lumbar puncture, and the signs of demyelination at the ENMG. The diagnosis of Gougerot-Sjögren’s syndrome in our three patients was established on the basis of the 2016 ACR/EULAR criteria. Indeed, the anti-SSA antibodies (Ro) were positive in our 3 patients with a biopsy of the salivary glands which showed stage 3 in the first patient and stage 4 in the two others. Corticosteroid therapy and immunosuppressive treatment resulted in a favourable clinical evolution on the neurological and general levels. Conclusion: Gougerot-Sjögren’s syndrome is an autoimmune exocrinopathy that may present with peripheral neuropathy, which may precede the diagnosis of Sjögren’s syndrome, be concomitant or occur during the course of the disease.展开更多
<div style="text-align:justify;"> <span style="font-family:Verdana;"><strong>Background:</strong> The association of primary Sj<span style="white-space:nowrap;"...<div style="text-align:justify;"> <span style="font-family:Verdana;"><strong>Background:</strong> The association of primary Sj<span style="white-space:nowrap;">ö</span>gren syndrome (PSS) and AA amyloidosis is a rare occurrence. <strong>Objective: </strong>To describe the phenotype of patients with this association through our two cases and a literature review. <strong>Materials and methods:</strong> A report of two cases of AA amyloidosis complicating primary Sj<span style="white-space:nowrap;">ö</span>gren syndrome with a literature review. <strong>Results:</strong> Eight patients of Primary Sj<span style="white-space:nowrap;">ö</span>gren’s Syndrome complicated by AA amyloidosis were studies. Six cases were reported in the literature by consulting several databases. 50% of patients had a positive immunological assessment, three cases with kidney damage, and three cases lung damage. <strong>Conclusion: </strong>The immunological activity in the Primary Sjogren’s Syndrome requires the search not only a lymphoma but also AA amyloidosis apart from any clinical or biological chronic inflammation.</span> </div>展开更多
基金Supported by National Natural Science Foundation of China(No.82471046)the Joint Medical Research Project of Chongqing Health Commission and Science and Technology Bureau(No.2023GDRC004)the Program for Youth Innovation in Future Medicine of Chongqing Medical University(No.W0185).
文摘AIM:To investigate the expression of interferon regulatory factors(IRFs)in peripheral blood mononuclear cells(PBMCs)of patients with Sjögren’s syndrome-related dry eye(SSDE)and to explore their correlation with clinical features,dendritic cell activation,and serological indicators.METHODS:A total of 53 SSDE patients and 62 non-Sjögren’s syndrome dry eye(NSSDE)patients were enrolled.Demographic and clinical data were collected,and comprehensive ophthalmic examinations were performed,including the ocular surface disease index(OSDI)questionnaires,Schirmer I test(SIT),tear break-up time(TBUT),corneal fluorescein staining score(CFS),and in vivo confocal microscopy(IVCM).PBMCs were isolated,and IRFs expression levels were analyzed using Western blotting(WB)and quantitative real-time polymerase chain reaction(qRT-PCR).Serological indicators,including antinuclear antibodies(ANA)and anti-Ro60,anti-Ro52,and anti-La autoantibodies,were detected.Statistical analyses evaluated correlations between IRFs expression and clinical parameters.RESULTS:Compared to NSSDE,the relative mRNA and protein expression of the IRF-8 was significantly upregulated in patients with SSDE(P<0.001),whereas no significant differences were observed in IRF-1,IRF-3,IRF-5,and IRF-7(P=0.12,P=0.10,P=0.66,P=0.96).Correlation analysis revealed that IRF-8 expression was positively associated with CFS and OSDI scores(r=0.57,r=0.38,both P<0.05).Moreover,IRF-8 expression correlated with corneal dendritic cell(DC)density and size,and the number of dendrites(r=0.43,r=0.40,r=0.65,all P<0.05).IRF-8 expression was significantly elevated in patients positive for anti-Ro60,anti-Ro52 and anti-La autoantibodies(P<0.05).CONCLUSION:In SSDE,IRF-8 is upregulated and associated with clinical features,DC activation,and serological indicators.These findings suggest that IRF-8 plays a critical role in SSDE pathogenesis and may serve as a potential therapeutic target for diagnosis and treatment.
基金supported by the National Natural Science Foundation of China(grants 31972908,81991500,81991502,and 32030010)Beijing Natural Science Foundation(grant 7202082).
文摘Tricellulin,a key tricellular tight junction(TJ)protein,is essential for maintaining the barrier integrity of acinar epithelia against macromolecular passage in salivary glands.This study aims to explore the role and regulatory mechanism of tricellulin in the development of salivary gland hypofunction in Sjögren’s syndrome(SS).Employing a multifaceted approach involving patient biopsies,non-obese diabetic(NOD)mice as a SS model,salivary gland acinar cell-specific tricellulin conditional knockout(TricCKO)mice,and IFN-γ-stimulated salivary gland epithelial cells,we investigated the role of tricellulin in SS-related hyposalivation.Our data revealed diminished levels of tricellulin in salivary glands of SS patients.Similarly,NOD mice displayed a reduction in tricellulin expression from the onset of the disease,concomitant with hyposecretion and an increase in salivary albumin content.Consistent with these findings,TricCKO mice exhibited both hyposecretion and leakage of macromolecular tracers when compared to control animals.Mechanistically,the JAK/STAT1/miR-145 axis was identified as mediating the IFN-γ-induced downregulation of tricellulin.Treatment with AT1001,a TJ sealer,ameliorated epithelial barrier dysfunction,restored tricellulin expression,and consequently alleviated hyposalivation in NOD mice.Importantly,treatment with miR-145 antagomir to specifically recover the expression of tricellulin in NOD mice significantly alleviated hyposalivation and macromolecular leakage.Collectively,we identified that tricellulin deficiency in salivary glands contributed to hyposalivation in SS.Our findings highlight tricellulin as a potential therapeutic target for hyposecretion,particularly in the context of reinforcing epithelial barrier function through preventing leakage of macromolecules in salivary glands.
文摘Introduction: Glomerular damage during Gougerot-Sjgren syndrome is much rarer than interstitial damage, and is essentially extra-membranous and membrano-proliferative glomerulonephritis. Observation: We report the case of a 44-year-old woman with primary Sjgrens syndrome, confirmed by clinical dryness syndrome, positive anti-SSA and anti-SSB antibodies, and a salivary gland biopsy revealing grade 4 lymphocytic sialadenitis according to CHISHOLMs classification. Later, the patient developed nephrotic syndrome, along with hypertension. Renal function remained normal with a creatinine level of 9.3 mg/l, and hematuria was absent. Only antinuclear antibodies tested positive, while anti-PLA2R antibodies were negative. A renal biopsy was performed, which was complicated on the same day by hemodynamic instability with hematuria. Renal CT scan with contrast injection revealed a posterior perirenal hematoma without contrast extravasation. Additionally, bilateral renal vein thrombosis was incidentally discovered, suggesting extramembranous glomerulonephritis. The patients hemodynamic status stabilized after fluid resuscitation with isotonic saline solution (0.9%), without the need for blood transfusion. Renal biopsy confirmed extramembranous glomerulonephritis with interstitial fibrosis and minimal tubular atrophy. The initial etiological assessment was negative. The patient was started on oral corticosteroids, angiotensin-converting enzyme inhibitors, and therapeutic anticoagulation for renal vein thrombosis. The patients condition improved, with the disappearance of the syndrome and spontaneous regression of the hematoma. Discussion: The association of nephrotic syndrome and renal vein thrombosis primarily suggests glomerulopathy, in particular extra-membranous glomerulonephritis. Sjgrens syndrome can be associated with extra-membranous glomerulonephritis without being its direct cause. Like, it is possible that it is a cause of glomerulonephritis, essentially extra membranous and membrano-proliferative. Conclusion: Sjgrens syndrome is generally underestimated cause of glomerulonephritis, which should be considered in cases of extra-membranous glomerulonephritis.
文摘BACKGROUND Celiac disease(CD)is a systemic,chronic immune-mediated disease triggered by gluten ingestion in genetically-susceptible individuals,with a prevalence of 1%worldwide.Sjogren's syndrome(SS)is also a systemic autoimmune disease,mainly characterized by ocular and oral sicca symptoms and signs.Sharing a common genetic background,CD and SS are known associated autoimmune diseases,but currently available guidelines are not reporting it.CASE SUMMARY We report the case of a 39-year-old woman,who was in the care of her rheumatologist for 2 years with SS.On routine follow-up she was found to have iron deficiency,without anemia.She had no gastrointestinal complaints and denied any obvious source of blood loss.IgA tissue transglutaminase antibodies were positive and endoscopy with duodenal biopsies revealed crypt hyperplasia and villous atrophy.A diagnosis of CD was set and gluten-free diet was recommended.CONCLUSION We present a review of existing data in the literature regarding the association of the two diseases,summarizing prevalence studies of CD in SS patients and the other way around.Screening recommendations and future research perspectives are also discussed,highlighting clinically relevant unanswered questions with respect to the association of CD with SS.
基金Supported by the National Natural Science Foundation of China,No.81801600。
文摘BACKGROUND Although the presentations of Sjögren’s syndrome(SS)are variable,ranging from mild dryness to wider systemic involvement,ranulas as early clinical signs were scarcely reported.Here,we present an adult patient with SS,who developed a unilateral simple ranula and was diagnosed primary SS 3 years later.We also provide a review of cases of SS and ranulas from 1980 to 2020.CASE SUMMARY A 22-year-old girl was found to have a left painless floor-of-mouth lesion 3 years ago,without obvious trauma or inducement.The diagnosis of a unilateral(left)simple ranula was made,and the ranula was surgically treated.Within 3 years after the ranula surgery,she developed acute lymphadenectasis in unilateral parotid twice without inducement,and ultrasonic examination revealed diffuse lesions in bilateral parotids and submandibular glands,which strongly suggested SS.Serologic tests and the unstimulated whole saliva flow rate confirmed the SS diagnosis.CONCLUSION Our study underlines that ranulas are early clinical signs of SS.As early diagnosis and early intervention of SS are important to obtain better outcomes,our findings underline the need for histopathological test after sublingual adenectomy and imaging detection of exocrine glands for the patients with ranulas.
基金Supported by the Lanzhou Science and Technology Plan Project,No.2018-3-48Lanzhou Talent Innovation and Entrepreneurship Project,No.2019-RC-35and 2019 Special Fund for Doctoral Training of Lanzhou University Second Hospital,No.YJS-BD-15.
文摘BACKGROUND Primary Sjögren's syndrome(pSS)concomitant with autoimmune hemolytic anemia(AIHA)but without eye and mouth dryness is exceedingly rare.Iguratimod(IGU)has been widely used in the treatment of pSS.However,there are few reports about the application of IGU in pSS concomitant with AIHA.CASE SUMMARY Here,we present the case of a patient with pSS concomitant with AIHA but without eye and mouth dryness.The patient was initially diagnosed with hyperplastic anemia and AIHA while pSS was missed,and was finally diagnosed with pSS concomitant with AIHA.The patient was treated with IGU along with prednisone and hydroxychloroquine,and her hemoglobin,reticulocytes and IgG returned to normal levels.CONCLUSION IGU was effective for and well tolerated by our patient with pSS concomitant with AIHA,and may be a promising therapy for the treatment of this disease.
文摘Introduction: Sjögren’s syndrome is an autoimmune epithelitis with various extraglandular signs, among which are neurological, with a variable frequency according to studies. We report three cases of peripheral neuropathy revealing Gougerot-Sjögren’s syndrome, collected in the Neurology Department of the Fann University Hospital in Dakar (Senegal). Observations: The first patient, aged 48 years, presented with a length-dependent sensitivomotor polyneuropathy associated with retrobulbar optic neuritis, with dry eyes and dry mouth noticed by the patient for several years. The second patient, aged 28 years, was admitted to the hospital with chronic generalized paresthesia in the context of xerostomia and xerophthalmia. The results of the clinical examination and the electroeneuromyogram were in favour of pure sensory neuronopathy. The third patient was 32 years old female, with a history of thyroidectomy and acute inflammatory demyelinating polyneuropathy (AIDP), who was seen for acute ascending flaccid tetraplegia with facial diplegia, preceded by diffuse paresthesia. The diagnosis of recurrence of acute demyelinating polyradiculonueropathy was retained in view of the rapidly increasing character of the deficit, the hyperproteinorachy at the lumbar puncture, and the signs of demyelination at the ENMG. The diagnosis of Gougerot-Sjögren’s syndrome in our three patients was established on the basis of the 2016 ACR/EULAR criteria. Indeed, the anti-SSA antibodies (Ro) were positive in our 3 patients with a biopsy of the salivary glands which showed stage 3 in the first patient and stage 4 in the two others. Corticosteroid therapy and immunosuppressive treatment resulted in a favourable clinical evolution on the neurological and general levels. Conclusion: Gougerot-Sjögren’s syndrome is an autoimmune exocrinopathy that may present with peripheral neuropathy, which may precede the diagnosis of Sjögren’s syndrome, be concomitant or occur during the course of the disease.
文摘<div style="text-align:justify;"> <span style="font-family:Verdana;"><strong>Background:</strong> The association of primary Sj<span style="white-space:nowrap;">ö</span>gren syndrome (PSS) and AA amyloidosis is a rare occurrence. <strong>Objective: </strong>To describe the phenotype of patients with this association through our two cases and a literature review. <strong>Materials and methods:</strong> A report of two cases of AA amyloidosis complicating primary Sj<span style="white-space:nowrap;">ö</span>gren syndrome with a literature review. <strong>Results:</strong> Eight patients of Primary Sj<span style="white-space:nowrap;">ö</span>gren’s Syndrome complicated by AA amyloidosis were studies. Six cases were reported in the literature by consulting several databases. 50% of patients had a positive immunological assessment, three cases with kidney damage, and three cases lung damage. <strong>Conclusion: </strong>The immunological activity in the Primary Sjogren’s Syndrome requires the search not only a lymphoma but also AA amyloidosis apart from any clinical or biological chronic inflammation.</span> </div>
