AA amyloidosis associated with morbid obesity (clinical case)

Abstract

We present the case of a 45-year-old woman who was hospitalized due to severe macrocytic anemia and renal failure. The patient presented a morbid obesity.

The immunological study showed anti-ENA anti-SSA (Ro52) positive, with negative antinuclear antibodies. Also in the proteinogram (serum immunofixation) the presence of monoclonal bands IgG lambda and IgG kappa, monoclonal component 7.2% (4.68 g/L), with elevation of free light chains (kappa 95.94 mg/L (3.3–19.4), evidenced, lambda 145.17 mg/L (5.71–26.3)).

The bone marrow study showed an infiltration of 5% of plasma cells and positive for AA amyloid. Finally, a percutaneous renal biopsy was performed, which again showed amyloid infiltration.

In the genetic study, 2 mutations of the family Mediterranean fever gene (MEFV) have been identified.

Secondary AA amyloidosis has been described associated with obesity, in addition to a percentage of cases of unknown etiology.

Resumen

Presentamos el caso de una mujer de 45 años que fue hospitalizada debido a una anemia macrocítica severa e insuficiencia renal. El paciente presentaba una obesidad mórbida.

El estudio inmunológico mostró positividad para anti-ENA, anti-SSA (Ro52) y negatividad para anticuerpos antinucleares. También en el proteinograma (inmunofijación sérica) se detectó la presencia de bandas monoclonales IgG lambda e IgG kappa, con un componente monoclonal del 7,2% (4,68 g/l) y la elevación de cadenas ligeras libres (kappa 95,94 mg/l [3,3-19,4]; lambda 145,17 mg/l [5,71-26,3]).

El estudio de biopsia de médula ósea mostró una infiltración del 5% de células plasmáticas y positividad para amiloide AA. Finalmente, se realizó una biopsia renal que nuevamente mostró infiltración amiloide.

En el estudio genético se identificaron 2 mutaciones del gen de la fiebre mediterránea familiar (MEFV).

La amiloidosis secundaria AA se ha descrito asociada a la obesidad, además de un porcentaje de casos de etiología desconocida.

Introduction

Recent decades have led to the discovery of different amyloid types. Initially, amyloid was thought to represent a single entity. Are associated with clinically different diseases, including neoplasia and inflammatory, degenerative, genetic, and iatrogenic processes. Currently, 36 different protein, have been shown to be amyloidogenic.

An amyloid fibril protein is a protein that is deposited as insoluble fibrils, mainly in the extracellular spaces of organs and tissues as a result of sequential changes in protein folding that result in a condition known as amyloidosis.

An amyloid fibril protein occurs in tissue deposits as rigid, non-branching fibrils approximately 10 nm in diameter. The fibrils bind the dye Congo red and exhibit green, yellow or orange birefringence when the stained deposits are viewed by polarization microscopy. When isolated from tissues and analyzed by X-ray diffraction, the fibrils exhibit a characteristic cross β diffraction pattern.¹

The current amyloid nomenclature is based on the chemical structure of the fibril protein. Thus, a letter A (for amyloid) is followed by a suffix that is an abbreviated form of the precursor protein's name.

The form of amyloidosis AL currently represents about 80% of all forms of amyloidosis. The amyloidosis associated with an underlying plasma cell dyscrasia, when amyloid is derived from immunoglobulin light chains, the amyloid fibril is designated as AL and the disease is AL amyloidosis. In amyloidosis derived from the acute phase reactant serum amyloid A protein (SAA), the amyloid type is designated AA. Classifications of amyloid of different types based solely on clinical features, currently is not recommended. In hereditary amyloidoses that are associated with mutations in the amyloid protein, in addition to the general amyloid designation, the location of the mutation and the amino acid substitution they must be indicated.2, 3 Amyloid deposits may be systemic or localized.

In the United States and the western world AL amyloidosis is the most common type of systemic amyloidosis, it constitutes 85% of all cases of systemic amyloidosis. The second most common type is AA amyloidosis. In case of AA amyloidosis, amyloid fibrils are derived from a truncated SAA, which is a major acute phase reactant. It is understood that SAA plays a role in inflammation and pathogen defense. Thus, AA amyloidosis develops in association with an enhanced and prolonged inflammation that leads to a sustained upregulated production of SAA and, subsequently, to its incomplete degradation, misfolding, and deposition in the tissues. In autoinflammatory diseases (including Crohn disease and familial Mediterranean fever) upregulated production of SAA is due to genetic defects in proteins involved in the modulation of the inflammatory response. This type amyloidosis affects the kidney and gastrointestinal tract. In case of nephritic syndrome, the most frequent clinical presentation is proteinuria.¹

Due to the great diversity of fibrillar amyloid proteins that can be deposited, the possibility of different concomitant processes in patients with amyloidosis, and the various modern treatments for the different entities, in addition to the histopathological confirmation of congofilia in the deposits, it is mandatory to perform the typing of the fiber specifically deposited. To carry out chemical identification of an amyloid fibril protein, immunohistochemistry, Western blotting, mass spectrometry, after or without combination with laser capture, amino acid sequencing, and immune-electron microscopy are useful techniques.

The immunohistochemical technique, which uses specific monoclonal antibodies, is an effective method for the classification of amyloidosis that has shown a very high sensitivity and specificity of 100%.

We present the case of a patient with AA amyloidosis who has not been clinically associated with any chronic infectious, inflammatory or neoplastic disease.