Development Of AA Amyloidosis Research Articles

The relation between C-reactive protein and serum amyloid A in patients with autoinflammatory diseases

BackgroundAutoinflammatory diseases are rare disorders of the innate immune system characterized by fever and other signs of inflammation. A feared complication of autoinflammatory diseases is the development of AA amyloidosis. AA amyloidosis is caused by extracellular deposition of soluble serum amyloid A (SAA) proteins as insoluble amyloid fibrils leading to organ damage. Prolonged high levels of SAA are a prerequisite to develop AA amyloidosis. Since measurement of SAA is relatively expensive and sometimes unavailable, C-reactive protein (CRP) is often used as a surrogacy marker to test for inflammation.ObjectiveThe aim of this research is to evaluate the possible relation between CRP and SAA.MethodsA retrospective cohort of patients with autoinflammatory diseases (n = 99) where SAA and CRP blood testing was performed in the period between 2015 and 2021 in the University Medical Centre in Groningen was used to investigate the correlation between CRP and SAA.ResultsCRP and SAA have a high correlation (rho = 0.755, p < 0.001). A CRP value below 0.45 mg/L results in 100% sensitivity for SAA below 4 mg/L. CRP below 5 mg/L is a good predictor of SAA below 4 mg/L with 85.4% sensitivity and 83.6% specificity. Only prednisone and erythrocyte sedimentation rate (ESR) significantly influence the relation between CRP and log10SAA.ConclusionThere was a significant correlation between CRP and SAA in our retrospective cohort. CRP levels below 5 mg/L proved to be highly predictive of SAA levels below 4 mg/L. This may not be true for patients on steroids.

Development of AA Amyloidosis in a Patient with Psoriasis: A Case Report

Psoriasis is a chronic, recurrent, inflammatory and common skin disease of unknown aetiology. Amyloidosis is defined as a heterogeneous group of diseases in which generally soluble plasma proteins accumulate in the extracellular space as insoluble abnormal fibrils. Type AA amyloidosis is a late and severe complication of chronic inflammatory disorders and some chronic infections. Although psoriasis is a common inflammatory skin disease, the development of amyloidosis is rare. Herein, we presented a case of psoriasis who developed AA-type amyloidosis.

Serum amyloid A as a marker of ankylosing spondylitis activity

Serum amyloid A protein A (SAA) is a normal serum protein (serving as a precursor of fibrillar tissue protein AA), synthesized in the liver and a rapidly responding marker of the acute phase of inflammation. A constant high concentration of SAA is one of the factors in the development of AA-amyloidosis. As a rule, secondary amyloidosis develops in patients with long-term and poorly controlled inflammatory diseases, including rheumatic diseases, one of which is ankylosing spondylitis (AS).Objective: to assess the level of SAA in AS patients and its relationship with indicators of disease activity.Patients and methods. The study included 124 patients with AS who met the modified New York 1984 criteria. The disease activity and functional status of patients were assessed according to the recommendations of Russian experts. SAA and CRP, ESR in blood serum were measured in all patients.Results and discussion. The median SAA concentration was 12.5 mg/L [4; 71.6]. Of 124 patients, 31% had SAA levels &lt;5 mg/L and 69% had &gt;5 mg/L. A strong correlation was found between the levels of SAA and CRP (r=0.80, p&lt;0.000001), no significant relationship was found between SAA and ESR (r=0.31, p=0.92). The correlation between the AS activity according to the BASDAI index and SAA was weak (r=0.3, p&lt;0.002), the correlation with ASDAS-CRP was moderate (r=0.54, p&lt;0.00001).Conclusion. A statistically significant relationship was found between SAA and CRP levels, as well as the AS activity indices. Research has shown that SAA can be used as one of the markers of inflammation in AS.

Successful Treatment of AA Amyloidosis in Ankylosing Spondylitis Using Tocilizumab: Report of Two Cases and Review of the Literature.

Historically, secondary amyloidosis has been a feared complication of chronic inflammatory conditions. The fibril protein AA derives from the acute phase reactant serum amyloid A (SAA). Long-term elevation of SAA levels remains a major risk factor for the development of AA amyloidosis in rheumatic diseases, and the prognosis may be unpredictable. Nowadays, with increased availability of effective biological agents, the incidence of AA amyloidosis seems to be declining. Still, genetically predisposed subjects with slowly progressive disease and mild symptoms combined with ongoing systemic inflammation may be at risk. Interleukin-6 (IL-6) is one of the drivers of SAA release and effectiveness of the humanized anti-IL-6 receptor antibody tocilizumab (TCZ) for the treatment of AA amyloidosis has been observed in some rheumatic conditions. Herein, we report two male subjects with longstanding ankylosing spondylitis (AS) complicated by renal amyloidosis who received TCZ with rapid and beneficial effects regarding inflammation and proteinuria. To the best of our knowledge, the use of TCZ in AS patients with this extra-articular manifestation has not previously been described. The paper includes histopathology, clinical follow-up, and longitudinal data of the two cases along with a comprehensive review of relevant literature. Mechanisms behind amyloid-mediated tissue damage and organ dysfunction are discussed. Altogether, our data highlight that blocking IL-6 signaling may represent a promising therapeutic option in patients with renal AA amyloidosis.

Genotyping of MEFV and SAA1 Genes and Their Correlation to the AA-Amyloidosis Development

Background: Familial Mediterranean fever (FMF) is the most common autoinflammatory disease caused by recessive mutations in the MEFV gene. If not treated, FMF patients may develop renal AA-amyloidosis that leads to renal failure and death. Both mutations and polymorphisms in MEFV and SAA1 genes, respectively, have been associated with AA-amyloidosis in several populations. In Algeria, as FMF is still under-estimate and misdiagnosed, genetic data on renal complication are largely lacking. We thus explored the contribution of MEFV and SAA1 loci in the development of amyloidosis in Algerian patients with FMF. Methods: This study included 64 unrelated FMF patients (21 without and 43 with renal amyloidosis) and 13 healthy controls. The entire exon 10 was sequenced after PCR amplification to detect MEFV mutations. Genotypes of SAA1 locus (SAA1.1, SAA1.5, and SAA1.3) were determined by PCR-RFLP (restriction fragment length polymorphism). Results: Analyze of MEFV gene showed that the percentage of homozygous for p.M694I mutation was significantly higher in patients with amyloidosis compared to patients without amyloidosis (p=0.032). The SAA1.1/1.1 genotype was significantly predominant in patients with amyloidosis compared to those without AA-amyloidosis (p=0.001) and controls (0.001). The SAA1.5/1.5 genotype was identified only in patients without amyloidosis and controls. The most patients with renal complications were homozygous for p.M694I and SAA1.1 alleles. Conclusion: Our data suggest a positive correlation between the p.M694I/M694I and SAA1.1/1.1 genotypes and the development of AA-amyloidosis secondary to FMF in Algerian patients.

Familial mediterranean fever: clinical case

Background. Familial Mediterranean fever (FMF) is the brightest exponent of autoinflammatory diseases. FMF usually occurs to people of Mediterranean origin (Jews, Armenians, Azerbaijanis, Arabs, Kurds, Greeks, Turks and Italians). This is a hereditary disease with the autosomal recessive inheritance. Includes history of research, epidemiology FMF, variants of the disease course, methods of treatment.&#x0D; Clinical case description. A 61-year-old woman arrived complaining of weakness, fever, joint pain. First sign of disease showed at 20-years-old. When she came in: WBC 20.1–109/l, HGB 6.7 g/ml, ESR 60 mm/h, CRP 100 mg/l, CRP 202 μmol/L, UREA 19.7 mmol/L. Quantity of protein in one liter of urine 0.160 g. Ultrasonic signs of pyelectasis in both kidneys. The diagnosis was made on the basis of characteristic attacks of fever, polyarthritis, thoracalgia of Armenian nationality patient. The diagnosis was confirmed by the detection of amyloidosis and genetic data.&#x0D; Conclusion. Knowledge of the FMF clinical profile is important for differential diagnosis with many acute conditions, e.g. acute abdomen, myocardial infarction, pneumothorax, rheumatic diseases. It is important to remember that untimely diagnosis and improper treatment lead to the development of AA-amyloidosis (30–40%) with the outcome of renal failure.

Serum amyloid A forms stable oligomers that disrupt vesicles at lysosomal pH and contribute to the pathogenesis of reactive amyloidosis

Serum amyloid A (SAA) is an acute-phase plasma protein that functions in innate immunity and lipid homeostasis. SAA is a protein precursor of reactive AA amyloidosis, the major complication of chronic inflammation and one of the most common human systemic amyloid diseases worldwide. Most circulating SAA is protected from proteolysis and misfolding by binding to plasma high-density lipoproteins. However, unbound soluble SAA is intrinsically disordered and is either rapidly degraded or forms amyloid in a lysosome-initiated process. Although acidic pH promotes amyloid fibril formation by this and many other proteins, the molecular underpinnings are unclear. We used an array of spectroscopic, biochemical, and structural methods to uncover that at pH 3.5-4.5, murine SAA1 forms stable soluble oligomers that are maximally folded at pH 4.3 with ∼35% α-helix and are unusually resistant to proteolysis. In solution, these oligomers neither readily convert into mature fibrils nor bind lipid surfaces via their amphipathic α-helices in a manner typical of apolipoproteins. Rather, these oligomers undergo an α-helix to β-sheet conversion catalyzed by lipid vesicles and disrupt these vesicles, suggesting a membranolytic potential. Our results provide an explanation for the lysosomal origin of AA amyloidosis. They suggest that high structural stability and resistance to proteolysis of SAA oligomers at pH 3.5-4.5 help them escape lysosomal degradation, promote SAA accumulation in lysosomes, and ultimately damage cellular membranes and liberate intracellular amyloid. We posit that these soluble prefibrillar oligomers provide a missing link in our understanding of the development of AA amyloidosis.

Anti-IL1ß-monoclonal antibody in a patient with Muckle-Wells Syndrome and renal transplantation - five years experience

Background The Muckle-Wells syndrome (MWS) is a rare inherited disease and belongs to the group of cryopyrin-associated periodic syndromes (CAPS). Recurrent fever attacks, myalgia, arthralgia, urticarial rash, headache, conjunctivitis, sensorineural deafness and a severe fatigue syndrome are the typical symptoms of MWS. Due to an unregulated production of IL1 a continuous formation of serum amyloid leads ultimately to the development of AA-amyloidosis, which is life-threatening and in some cases the fatal complication of MWS.

Predictors of AA amyloidosis in familial Mediterranean fever.

The aim of the study was to evaluate the clinical and genetic predictors of AA amyloidosis in patients with familial Mediterranean fever (FMF). We retrospectively studied 170 Armenian patients who were admitted to the two tertiary centers in 2003-2014. The diagnosis of amyloidosis that was suspected clinically (new proteinuria or nephrotic syndrome) was confirmed histologically. Screening for MEFV gene mutations was performed in 70 patients. The most common genotype was M694V/M694V (in 36% of patients). Biopsy-proven AA amyloidosis was found in 102 (60%) of 170 patients. AA amyloidosis was diagnosed in 17 (68%) of 25 patients with homozygous M694V mutation, 17 (53%) of 32 patients with heterozygous M694V allele and 4 (31%) of 13 patients with other MEFV gene mutations. The M694V homozygosity and heterozygosity were associated with increased risk of AA amyloidosis, but this association did not reach statistical significance (odds ratio 2.43; 95% CI 0.87-6.76, and 3.33; 0.91-12.1, respectively). Male gender, early onset of disease, severity of FMF, frequent attacks, peritonitis, pleuritis and erysipelas-like erythema also did not predict AA amyloidosis development. Recurrent arthritis was the only clinical finding that was significantly associated with AA amyloidosis (odds ratio 2.28; 95% CI 1.17-4.42). Involvement of the joint synovial membrane, that is capable of active serum amyloid A production, is the main predictor of renal amyloidosis in FMF.

Systemic AA amyloidosis as a prion-like disorder

Amyloidosis is a collective term for a group of disorders that induce functional impairment of organs and occurs through the accumulation of amyloid, or misfolded protein in beta-sheets. AA amyloidosis is a lethal systemic amyloidosis with SAA as the precursor protein, and is observed in various animal species, including humans. AA amyloidosis can be induced artificially by continuously administering inflammatory stimuli in experimental animal models. In this process of experimental induction, the administration of AA amyloids from either the same or different species is known to markedly expedite AA amyloidosis development, and this is also termed transmission of AA amyloidosis. Similarly to prion disease, AA amyloidosis is considered to be transmitted via a “seeding-nucleation” process. In this manuscript, we reviewed the pathology and transmissibility of AA amyloidosis in animals.

AB0069 Mechanism Elucidation of Effectiveness of IL-6 Blockade for Reduction of SAA Production and Amyloid A Deposition in AA Amyloidosis Patients with RA

BackgroundAA amyloidosis is a serious complication of chronic inflammatory and infectious diseases resulting from the deposition of amyloid A protein. Serum amyloid A (SAA), a precursor molecule of AA protein...

P02-028 - Muckle-Wells syndrome and renal transplantation

The Muckle-Wells syndrome (MWS) is a rare inherited disease and belongs to the group of cryopyrin-associated periodic syndromes (CAPS). Recurrent fever attacks, myalgia, arthralgia, urticarial rash, headache, conjunctivitis, sensorineural deafness and a severe fatigue syndrome are the typical symptoms of MWS. Due to an unregulated production of IL1 a continuous formation of serum amyloid leads ultimately to the development of AA-amyloidosis, which is life-threatening and in some cases the fatal complication of MWS.

Renal amyloidosis secondary to hidradenitis suppurativa.

Hidradenitis suppurativa (HS), also known as Verneuil's disease [1] or acne inversa, is characterized by hyperkeratosis of the follicular epithelium, resulting in obstruction of the follicular stoma and chronic perifollicular inflammation with remissions and relapses, usually involving skin overlying the axillary, inguinal, perianal, perineal and inframammarian regions. It usually presents in the second and third decades of life, has a female preponderance, no racial predilection and a prevalence of 4%. Some causing factors might be obesity and related hormonal changes, hyperandrogenism, immunologic and genetic status, diet and smoking [2]. The diagnosis is based on the presence of relapsing lesions in typical anatomical regions. HS may be localized with chronic, relapsing, superficial papulopustular lesions, as it may be associated with deep, widespread abscesses, sinus tracts, fistulas, malignancies like squamous cell carcinoma and systemic complications like arthropathy or anaemia [3]. Besides topical and surgical care, therapy with antibiotics, steroids, retinoids and anti-TNF agents is usually considered. Rarely, amyloidosis may complicate the cutaneous disease [4]. A 42-year-old male was referred to our hospital for nephrotic syndrome. Three years before he was diagnosed with hidradenitis suppurativa when papulopustular lesions over the inguinal, perineal, perianal and axillary regions appeared. Over these 3 years, he had relapses with fever, extensive perineal tenderness and partial remissions leaving fibrotic scar tissue following treatment with topical steroids, keratolytics and antibiotics. His temperature was 37.1°C, blood pressure 140/90 mmHg and heart rate 76/min. He had bilateral pretibial pitting oedema and active bilateral inguinal, perineal, perianal and left axillary papulonodular and pustular, hyperaemic, tender lesions of 2–3 cm diameter, some of which fluctuating and draining, scar tissue, sinus tracts of the older lesions and bilateral inguinal and left axillary tender lymphadenopathies, the largest of which being 2 cm in diameter (Figure 1). Fig. 1. Left axillary active lesion (a) and sinus opening on the right lateral scrotal wall (b). No pathogen was isolated in the cultures of sinus openings and in his blood. Topical keratolytic and anti-inflammatory drugs combined with roxithromycin, rifampicin and clindamycin treatment for 1 month resulted in partial remission of the active lesions. A biopsy of the perineal skin revealed a non-specific inflammatory reaction without amyloid deposition. He was found to have a heterozygous M680I mutation of the exon 10 of the MEFV gene. Kidney biopsy revealed glomerular, perivascular and interstitial deposits that stained with Gentian violet, compatible with amyloidosis that was identified immunohistochemically as AA amyloidosis (Figure 2). Despite treatment with colchicine, kidney failure and proteinuria showed progression. Fig. 2. Interstitial eosinophilic amorphous amyloid deposition on haematoxylin and eosin stained section (a), strong positive glomerular and perivascular staining with amyloid A (b) and P component positivity (c). Amyloidosis and nephrotic syndrome are rare complications of HS with only four such cases in the literature [4]. One had rectal biopsy-proven symptomatic gastrointestinal amyloidosis, another one had infiltrative cardiomyopathy, assumed to be caused by amyloidosis. In our case, there was no amyloid deposition in skin biopsy and the abdominal computed tomography scan was normal with no hepatosplenomegaly. The patient did not have diarrhoea or gastrointestinal bleeding. His echocardiography was normal and he had no neuropathy. Although seen prevalently in endemic regions, carriers of MEFV gene mutations may have an increased risk of inflammatory diseases resulting in amyloidosis. The clinical course of inflammatory diseases like rheumatoid arthritis may be more severe in MEFV gene mutation carriers [5]. Despite its benign nature, hidrosadenitis must be early and actively treated as any chronic suppuration to avoid the development of AA amyloidosis, especially in carriers of the MEFV gene mutation.

AB0026 Genetic markers of secondary amyloidosis in belarusian patiens with rheumatoid arthitis

BackgroundThe development of secondary (AA) amyloidosis in rheumatoid arthritis (RA) is considered to be extensively determined by genotype characteristics. Serum amyloid A protein (SAA) is synthesized by liver under inflammatory...

Tocilizumab Treatment for Nephrotic Syndrome Due to Amyloidosis in Behcet’s Disease

Renal involvement is an unusual but significant Behcet´s disease (BD) complication and AA amyloidosis appears to be the most common etiology. IL-6 is a pro-inflammatory cytokine with an important role in AA amyloidosis development. Tocilizumab (TCZ) is a humanized anti-IL-6 receptor antibody that has emerged as an effective and specific treatment in AA amyloidosis secondary to chronic inflammatory disorders. We report on a patient diagnosed with BD who developed nephrotic syndrome caused by renal AA amyloidosis with an excellent response to TCZ therapy.

Renal AA-amyloidosis in intravenous drug users – a role for HIV-infection?

BackgroundChronic renal disease is a serious complication of long-term intravenous drug use (IVDU). Recent reports have postulated a changing pattern of underlying nephropathy over the last decades.MethodsRetrospective investigation including all patients with prior or present IVDU that underwent renal biopsy because of chronic kidney disease between 01.04.2002 and 31.03.2012 in the city of Frankfurt/Main, Germany.ResultsTwenty four patients with IVDU underwent renal biopsy because of progressive chronic kidney disease or proteinuria. Renal AA-amyloidosis was the predominant cause of renal failure in 50% of patients. Membranoproliferative glomerulonephritis (GN) was the second most common cause found in 21%. Patients with AA-amyloidosis were more likely to be HIV infected (67 vs.17%; p=0.036) and tended to have a higher rate of repeated systemic infections (92 vs. 50%; p=0.069). Patients with AA-amyloidosis presented with progressive renal disease and nephrotic-range proteinuria but most patients had no peripheral edema or systemic hypertension. Development of proteinuria preceded the decline of GFR for approximately 1–2 years.ConclusionsAA-amyloidosis was the predominant cause of progressive renal disease in the last 10 years in patients with IVDU. The highest rate of AA-amyloidosis observed was seen in HIV infected patients with IVDU. We speculate that chronic HIV-infection as well as the associated immunosuppression might promote development of AA-amyloidosis by increasing frequency and duration of infections acquired by IVDU.

Significance of SAA1 gene polymorphism in the development of AA amyloidosis in patients with rheumatoid arthritis in the Moscow population

Objective: to estimate the significance of SAA1 gene polymorphism in the development of AA amyloidosis in patients with rheumatoid arthritis (RA) in the Moscow population. Subjects and methods. The investigation included 57 RA patients treated at the clinic of the Research Institute of Rheumatology, Russian Academy of Medical Sciences, for histologically verified AA amyloidosis. In 41 of them, polymorphism of exon 3 of the SAA1 gene (SNP rs1136747 c.224T→C and SNPrs1136743 c.209C→T) was studied by polymerase chain reaction and restriction fragment length polymorphism analysis. Results. The carriage of the а/а genotype increases the likelihood of AA amyloidosis by 3 times in patients with RA (odds ratio (OR) = 3.0; p = 0.007). At the same time, the presence of allele β in the α/β genotype epistatically suppresses the action of allele α, by showing a 3-fold reduction in the risk of secondary amyloidosis in RA patients who were carriers of this genotype. Conclusion. The а/а genotype at the SAA1 locus is a risk factor for AA amyloidosis in patients with RA in the Moscow population; at the same time its presence of allele β in the heterozygous or homozygous state is a factor for preventing the development of this complication.

AA-amyloidosis in a kidney biopsy on top of pauci-immune crescentic glomerulonephritis.

In March 2011, a 56-year-old woman presented with fever of unknown origin accompanied with symmetric arthralgias and sinusitis. Her medical history was notable for diabetes mellitus Type 2, hypertension, smoking and multiple episodes of sinusitis. Admission blood chemistry tests revealed a leucocyte count of 14.3 × 109/L, a C-reactive protein (CRP) level of 4.4 mg/dL (<0.5 mg/dL), a creatinine level of 266.6 μmol/L and a blood urea nitrogen (BUN) level of 47 mg/dL. Urinalysis demonstrated gross proteinuria with a total protein/creatinine ratio of 6.4 g/g and nephritic sediment. Anti-nuclear, anti-GBM and MPO-ANCA antibodies were negative, Complement factor 3 and 4 in the normal range but PR3-ANCA antibodies were clearly detectable. Of note, computed tomography of her head and thorax displayed signs of pansinusitis but no pulmonary changes. A kidney biopsy was performed which revealed pauci-immune crescentic glomerulonephritis with crescent formation in 9 of 14 glomeruli. Most interestingly, glomeruli demonstrated Periodic Acid Schiff (PAS)-negative mesangial and perihilar deposits (Figure 1), which were positive for congo red (Figure 2, upper left insert). Immunohistochemistry revealed positivity for amyloid-P and amyloid-A (Figure 2, lower right insert). Electron microscopy confirmed fibrillary deposits consistent with amyloid (Figure 2). Amyloid was also present in arteriolar walls in the kidney. Since all other causes of AA-amyloidosis were excluded, the most probable underlying cause for AA-amyloidosis in our patient is long lasting granulomatosis with polyangiitis (Wegener’s). Since our patient suffered from multiple episodes of sinusitis in her medical history, it might be speculated that granulomatosis with polyangiitis (Wegener’s) was long-lasting, allowing the development of AA-amyloidosis. Fig. 1. A cellular crescent and PAS-negative perihilar and mesangial amyloid deposits (arrows) are present within one and the same glomerulum (PAS stain). Fig. 2. Typical fibrillary structure of amyloid deposits on transmission electron microscopy (uranyl acetate and lead citrate). Upper left inset: positive congo red staining of amyloid deposits. Lower right inset: positive immunohistochemistry for Amyloid A. Treatment of the patient was started with corticosteroids and intravenous cyclophosphamide. Because of a further decrease of kidney function requiring haemodialysis treatment, plasmapheresis was performed. After daily intensive plasmapheresis treatment for >2 weeks PR3-ANCAs became negative and fever as well as arthralgias resolved, but the patient’s kidney function has not recovered as yet.

Inflammatory Markers: Serum Amyloid A, Fibrinogen and C-Reactive Protein — A Revisited Study

The acute phase response is the part of the innate defence system of an animal against trauma, inflammation or infection. During this response, there is increased production and release of certain plasma proteins known as acute phase proteins, which include C-reactive protein (CRP), serum amyloid A (SAA) and fibrinogen (Fg). CRP consists of five identical subunits of 206 amino acids with a molecular weight of approximately 23 kDa. There is strong evidence from numerous studies that CRP is a predictor of inflammation. The acute-phase protein serum amyloid A (SAA) is a clinically useful marker of inflammation. SAA plays not only an important role in the development of AA amyloidosis (an important complication of rheumatoid arthritis) but also interacts with events closely involved in the metabolic syndrome as a high- and low-grade inflammatory modulator. Fibrinogen (Fg) is a high molecular weight plasma adhesion protein and is a biomarker of inflammation. It is synthesized and assembled in hepatocytes and fibroblasts and when secreted into the circulation, its plasma half-life ranges from 3 to 4 days. Several cytokines, are involved in the induction of acute phase protein synthesis, but the mutual importance of these cytokines seems to be cell-type specific and to vary in various experimental settings. Here we revisited the classic acute phase proteins SAA, C-Reactive protein and fibrinogen in their role in inflammation and their interrelationship with some cytokines.

Recurrent AA Amyloidosis in a Kidney Transplant

Recurrent AA amyloidosis in a kidney transplant is rare, especially when the underlying inflammatory condition is controlled. We present a 59-year-old man who underwent a living donor kidney transplant 17 years ago for kidney failure due to AA amyloid nephropathy in the setting of long-standing Crohn disease. His Crohn disease was quiescent before and after the kidney transplant. Transplant function had been stable until a month before presentation, when he developed worsening proteinuria and decreased kidney function. A transplant biopsy showed recurrent AA amyloidosis despite excellent clinical and histologic control of Crohn disease.