Pénfigo herpetiforme con evolución a pénfigo foliáceo. Descripción de un caso / Pemphigus Herpetiformis With Progression To Pemphigus Foliaceus: A Case Report

No disponible

Correlation of immunological markers with graft vasculopathy development in heart transplantation.

This study examined the imbalance between T effector cells (Th1 defined as CD3+ interferonγ+) and T regulatory cells (Treg defined as CD4+CD25(high)FoxP3+) as a valuable albeit limited marker of cardiac allograft vasculopathy (CAV) after heart transplantation (HTx). CAV remains, with neoplasms, the most important cause of death in patients surviving the first year after HTx. It is an immune-mediated pathology, although nonimmune factors may also play a role. The process included concentric fibrous intima hyperplasia that narrows the entire length of the affected arteries. Coronary angiography is the usual method of diagnosis. Because a transplanted heart is a denervated organ, CAV is not diagnosed until the disease reaches an advanced stage, in which case transplantation is the only option for treatment. Although the host's immune response against an allogeneic graft is the major cause of endothelial dysfunction, the objective of this study was to detect anti-allogeneic responses on peripheral blood, seeking to identify signs of CAV before classical methods to predict outcomes in HTx recipients. CD3, CD4, CD8, CD19, CD56, Th1, and the Treg mononuclear cell populations were studied in 37 de novo and 20 long-term (more than 3 years) HTx patients as well as 20 healthy volunteers using flow cytometry. A progressive increase in CD8 and Th1 percentages and decrease in the CD4 population were detected during follow-up. Although Th1 changes also reflect processes not related to CAV receiver operating characteristics analysis of Th1/Treg ratio showed an area under the curve of 0.976, with an estimated sensitivity of 100% and specificity of 90%. The positive prediction value was 58.8% and the negative prediction value, 100%. These results prove that the Th1/Treg ratio was an important marker to following host immune response after HTx. The results confirm the need to test other T lymphocyte subsets.

Assessment of immunological markers as mediators of graft vasculopathy development in heart transplantation.

Heart transplantation (HT) remains the treatment of choice for patients with end-stage heart failure. Cardiac allograft vasculopathy (CAV), a diffuse form of coronary atherosclerosis, is the major cause of death after the first year of HT. CAV is thought to be multifactorial in origin. Although nonimmune factors may play a role in CAV development, it is primarily an immune-mediated disease. CAV is diagnosed by routine annual coronary angiography, and usually when diagnosed, the disease is advanced. There is a need to develop noninvasive surrogate markers for early detection. For this purpose, careful immune monitoring and graft histologic assessment are mandatory. The main objective of this study was the assessment of immunologic markers as mediators of CAV development in HT. Flow cytometry was performed to assess peripheral blood mononuclear cell populations forming CD3, CD4, CD8, CD19, CD56, Th1 (CD3+IFNγ+) or Treg (CD4+CD25(high)FoxP3+) markers among 20 de novo HT recipients. The control group included 13 patients who were more than 2 years post-HT (four with and nine without CAV) as well as 20 healthy subjects. CAV-related events over 2 years' follow-up correlated with the Th1/Treg ratio. An increased Th1 lymphocyte percentage was detected over the follow-up. Patients with medium and high Th1/Treg ratios showed higher acute rejection scores as well as greater incidences of CAV. These results indicated that the Th1/Treg ratio may represent a valuable marker to monitor allospecific T-cell responses in peripheral blood. Changes in the Th1/Treg ratio may help in the early detection of patients at risk for CAV. More studies with longer follow-up are needed to confirm these preliminary results.

Bullous pemphigoid and multiple sclerosis: a report of two cases with ELISA test.

We report two patients with longstanding multiple sclerosis (MS) who developed vesicles and bullae consistent with the diagnosis of bullous pemphigoid (BP). Both patients showed linear IgG at the dermal-epidermal junction, located on the epidermal side of patients' skin previously treated with 1M NaCl. In the two cases, the ELISA test was positive for the extracellular fragment of BP 180. However, the indirect immunofluorescence test (IIF) was repeatedly negative. Therapy either with prednisone plus dapsone or prednisone alone was initiated and the disease was controlled after 23 and 15 months of therapy, in patients 1 and 2, respectively. However, the first patient had a flare-up 2 months after treatment was stopped. The association of MS and BP has been described previously in 35 cases. We compare our two cases with the 25 patients previously reported in detail in the literature. We emphasize the role of the ELISA test in establishing the diagnosis of BP.

Therapy of paraneoplastic pemphigus with Rituximab: a case report and review of literature.

Paraneoplastic pemphigus (PNP) is an autoimmune blistering disease with poor prognosis when associated with malignant neoplasm. We report the case of a patient with PNP associated with a CD20+ non-Hodgkin follicular lymphoma who was treated with Rituximab plus corticosteroids and short courses of cyclosporin. One and a half years after Rituximab therapy, oral ulcerations had cleared and oral methylprednisolone was slowly tapered down without further recurrences. In the course of the disease, the patient developed sepsis due to Listeria monocytogenes and viral infections by human herpes virus 1 and 3. At the end-stage of the disease she developed a cutaneous infection from Mycobacterium chelonae. The patient died 2 years and 7 months after the onset of PNP. Rituximab may be useful for PNP therapy, but further studies are necessary to confirm this hypothesis.

Thyroglobulin autoantibody levels below the cut-off for positivity can interfere with thyroglobulin measurement.

Antithyroglobulin antibodies can interfere with the measurement of thyroglobulin yielding spuriously high or low levels depending on the method used. Interference is unrelated to the antibody concentration and can occur at very low concentrations. We report a patient in whom antithyroglobulin antibodies below the cut-off for positivity nearly led to an incorrect diagnosis of thyrotoxicosis factitia.

Isolation and characterization of cDNA encoding the antigenic protein of the human tRNP(Ser)Sec complex recognized by autoantibodies from patients withtype-1 autoimmune hepatitis.

We previously described autoantibodies against a UGA serine tRNA-protein complex (tRNP(Ser)Sec) in patients with type-1 autoimmune hepatitis [1] and now define the specificity and frequency of this autoantibody and the DNA sequence encoding the tRNA(Ser)Sec-associated antigenic protein. The presence of anti-tRNP(Ser)Sec antibodies was highly specific for type-1 autoimmune hepatitis, as 47.5% of patients were positive compared with none of the control subjects. To characterize the antigenic protein(s), we immunoscreened a human cDNA library with anti-tRNP(Ser)Sec-positive sera. Two clones (19 and 13) were isolated. Clone 19 encodes a protein with a predicted molecular mass of 48.8 kD. Clone 13 is a shorter cDNA, almost identical to clone 19, which encodes a 35.9-kD protein. Expression of both cDNAs was accomplished in Escherichia coli as His-tagged recombinant proteins. Antibodies eluted from both purified recombinant proteins were able to immunoprecipitate the tRNA(Ser)Sec from a HeLa S3 cell extract, demonstrating their cross-reactivity with the mammalian antigenic complex. Recent cloning data relating to the target antigen(s) of autoantibodies in autoimmune hepatitis patients that react with a soluble liver antigen (SLA) and a liver-pancreas antigen (LP) have revealed that these two autoantibodies are identical and that the cloned antigen shows 99% amino acid sequence homology with tRNP(Ser)Sec.

Repeat direct immunofluorescence (DIF) test, using, 1 M NaCl treated skin, in the subepidermal autoimmune bullous diseases that contain IgG at the dermal epidermal junction.

Knowledge of autoimmune bullous diseases has greatly increased with the recognition of new entities, and the use of the direct immunofluorescence (DIF) using 1 molar per liter of sodium chloride (1 M NaCl) treated skin has been proposed. To estimate the frequency with which the different DIF patterns are present, we performed a systematic study of the skin or oral mucosa samples in which linear deposits of IgG at the basement membrane zone were detected by routine DIF in the last 6 years. The DIF tests were done on 56 samples before and after splitting the epidermis from the dermis with 1M NaCl. In 40 biopsies (72%) IgG was found on either the epidermal side or on both sides after 1M NaCl split. These cases corresponded to bullous pemphigoid (n=33), herpes gestationis (n=5) and cicatricial pemphigoid (n=2). In 6 cases (10.7%), IgG deposits were observed only on the floor, five corresponding to bullous pemphigoid and one to bullous pemphigoid-like eruption induced by amoxicillin. Repeat direct immunofluorescence using 1M NaCl split skin indicates that at least 12% of patients who were initially diagnosed as bullous pemphigoid, may in fact suffer a different entity, requiring other techniques to achieve the right diagnosis. This test can be a useful routine screening for autoimmune bullous diseases.

Antibodies against a novel nucleolar and cytoplasmic antigen (p105-p42) present in the sera of patients with a subset of rheumatoid arthritis (RA) with signs of scleroderma.

We identified three patients (two of them relatives) with RA and signs of scleroderma whose sera contained a high titre of IgG class antibodies against the nucleoli and the nucleoplasm of cells of different mammalian origins. Sera from these patients uniformly immunoprecipitated four polypeptides, from a 35S-methionine-labelled HeLa cell extract, whose mol. wts were 120, 105, 95 and 42 kD. Of these, the 95-kD protein was highly phosphorylated. By immunoblotting, these sera reacted with 105-, 95- and 42-kD proteins and affinity-purified antibodies from these, demonstrating that 105- and 95-kD proteins shared cross-reactive epitopes. Moreover, affinity-purified antibodies from each of these proteins immunoprecipitated the whole complex. Localization studies using immunoelectron microscopy and in vivo actinomycin-D-treated cells demonstrated that the 105-, 95- and 42-kD proteins were present in the granular component of the nucleolus and the nucleoplasm. In addition, the 105- and 95-kD were present in free polyribosomes as well as ribosomes attached to endoplasmic reticulum. Pulse/chase experiments strongly suggested that the complex was accomplished shortly after a 10-min pulse. It was preferentially present in the nucleus after a 2 h chase and in both nucleus and cytoplasm after a 5 h chase. We conclude that a protein complex with a main nucleolar distribution is a new autoantigen (p105-p42) recognized by autoantibodies present in the serum of a subgroup of patients with RA and scleroderma signs. These antibodies could be useful as diagnostic markers and as tools for further studies involving the biology of the nucleolus.

Bullous pemphigoid associated with acute glomerulonephritis.

We report an 82-year-old man who presented with bullous pemphigoid and who later developed an acute glomerulonephritis with the histopathological and immunofluorescence pattern of a postinfectious glomerulonephritis. Antibodies directed against 230 and 180 kDa bullous pemphigoid antigens were detected in the patient's serum by means of the immunoprecipitation technique. Staphylococcus aureus and methicillin-resistant S. aureus were isolated from the patient's skin. We consider that in this particular patient the cutaneous infection played a part in the development of the kidney complication.

B cells and monocytes are not developmentally affected in a case of reticular dysgenesis.

We report a patient with reticular dysgenesis (RD) who received an HLA-identical marrow graft and remained free of infection in spite of incomplete haematological recovery. Mixed chimerism was achieved and resulted from the presence of autologous B cells and monocytes and grafting of donor T cells. Granulocyte recovery was impaired. The B cells were CD5+ (B1 cells) and appeared to be functional, since serum immunoglobulin levels became normal after the graft. The findings described here suggest that in some cases the defect selectively affects different cell types, including the more abundant leucocyte populations, granulocytes and T lymphocytes. However, B cells and monocytes appear to be relatively spared in this case of RD. Furthermore, the present case may provide insight into the mechanism involved in the expansion of distinct B cell subpopulations (B1 and B2 cells).

Childhood sclerodermatomyositis: report of a case with the anti-PM/Scl antibody and mechanic's hands.

We report a boy with overlap manifestations of systemic sclerosis and dermatomyositis (sclerodermatomyositis) whose disease showed a changing clinical pattern, and who had mechanic's hands, which are a cutaneous marker of myositis. Serological studies revealed antinuclear antibodies with a homogeneous nucleolar pattern. The anti-PM-Scl antibody was demonstrated by immunoblotting. HLA typing was positive for HLA-DR3/4. After a follow-up period of 11 years, no progression to severe systemic involvement was detected, and aggressive treatment was not administered. The recognition of subsets of patients with homogeneous clinical features and serological markers should permit the recognition of separate conditions among overlap syndromes. This would have prognostic and therapeutic implications.

Generalized acquired cutis laxa associated with coeliac disease: evidence of immunoglobulin A deposits on the dermal elastic fibres.

Acquired cutis laxa (ACL) is an uncommon elastolytic disorder of unknown aetiology. In rare instances, ACL has been reported in association with autoimmune diseases and dermal deposit of immunoglobulins, suggesting that destruction of elastic tissue may be immunologically mediated. We report a 35-year-old man with generalized acquired cutis laxa (GACL) associated with a persistent papular erythematous eruption that histopathologically showed some resemblance to dermatitis herpetiformis. A marked reduction and degeneration of dermal elastic fibres was noted in biopsies from loose-hanging skin. Direct immunofluorescence from non-inflammatory loose skin revealed granular immunoglobulin A (IgA) deposits at the basement membrane zone and fibrillar IgA deposits in the dermal papillae. IgA deposits were also observed on the elastic fibres of the reticular dermis. Electron microscopy of skin from the submammary fold revealed fragmented elastic fibres, partial absence of peripheral microfibrils and abundant neutrophils, some of which were degranulated and adjacent to elastic fibres. Immunoelectron microscopy of an erythematous papule revealed IgA deposits around dermal elastic fibres. Antigliadin, antireticulin and antiendomysium antibodies were present. Jejunal biopsies showed a gluten-sensitive enteropathy. A possible IgA-mediated immune mechanism for the development of GACL in our patient is suggested.

The two isoforms of the 90-kDalton nucleolus organizer region autoantigen (upstream binding factor) bind with different avidity to DNA modified by the antitumor drug cisplatin.

It has been previously described that some proteins containing HMG boxes are able to bind more strongly to DNA modified with cis-diamminedichloroplatinum (II) (cisplatin) than to unmodified DNA. In the present study, we analyzed the interaction of cisplatin-modified DNA with the human autoantigen NOR-90 (UBF), a transcription factor that contains several HMG boxes. Using autoantibodies against NOR-90 to perform ELISA and immunoprecipitation, it was confirmed that NOR-90 (UBF) was able to bind cisplatin-modified DNA more avidly than unmodified DNA or trans-diamminedichloroplatinum(II) (transplatin) modified DNA. Moreover, by Southwestern, we observed that the 97 kDalton isoform of NOR-90 (UBF1) was able to bind cisplatin-modified DNA more strongly than the 94 kDalton isoform (UBF2); binding of unmodified DNA or transplatin-modified DNA was not detected with either isoform. Sera containing autoantibodies against NOR-90 did not inhibit, but increased the binding of NOR-90 to cisplatin-modified DNA.

Coexistence of two antisynthetases in a patient with the antisynthetase syndrome.

We describe the immunologic findings in a patient with the antisynthetase syndrome characterized by prominent arthritis, lung fibrosis, and subclinical myositis. At disease onset and during the followup, this patient's serum showed 2 different subsets of antisynthetase autoantibodies: anti-Jo-1, which reacted with histidyl-transfer RNA (tRNA) synthetase by immunoblot and inhibited its enzymatic function; and anti-0J, which immunoprecipitated the multi-enzyme complex of synthetases, and reacted with lysyl-tRNA synthetase by immunoblot. This is the first report of anti-Jo-1 and another antisynthetase antibody being found together in the same patient.